Path to Treatment and PreventionFebruary 9–10, 2015

National Institutes of HealthBethesda, MD

PROGRAM

#ADSummit15

ALZHEIMER’S DISEASE RESEARCH SUMMIT 2015

ALZHEIMER’S DISEASE RESEARCH SUMMIT 2015: PATH TO TREATMENT AND PREVENTION

SUMMIT PURPOSE AND GOALS

Need: Despite a substantial R&D investment for Alzheimer’s disease (AD) and advances made in our understanding of the disease pathogenesis, safe and effective treatments for AD patients are still lacking. This reflects the need for a change in how the academic, biopharmaceutical, and government sectors participating in AD research and therapy development generate, share, and use knowledge to propel the development of critically needed therapies. It is becoming apparent that real progress in developing effective therapies will require a transformation of the process of AD research and drug development into one that is participatory, collaborative, well-integrated, and iterative.

Goal: The central goal of the AD Research Summit 2015 is to continue the development of an integrated multidisciplinary research agenda necessary to address critical knowledge gaps and accelerate the discovery and delivery of efficacious treatments for AD patients at all stages of disease. Key to achieving this goal is the identification of resources/infrastructure and multi-stakeholder partnerships necessary to successfully implement this research agenda and strategies to empower patients and engage citizens.

Program Structure: The program will build on the foundation laid by the 2012 NIH AD Research Summit, the US National Alzheimer’s Project Act (NAPA)/National Plan to Address AD, and the 2013 G8 Global Dementia Summit. The agenda will be organized around 6 major themes presented in consecutive sessions which will evaluate issues of critical importance for identification and implementation of successful therapeutic interventions for Alzheimer’s disease. The program will begin with an overview of progress achieved in response to the recommendations of the 2012 NIH AD Research Summit, followed by three plenary lectures. Each of the 6 sessions will feature up to three brief presentations that will highlight key issues. Each set of presentations will be followed by a moderated panel discussion that will include the session speakers and 5-8 additional panelists with relevant expertise.

Speakers: The composition of speakers and panelists for each session will include representatives from academia, industry, federal agencies, private foundations and public advocacy groups working on Alzheimer’s and other complex diseases. Each session will bring together experts working in different disciplines since one of the major goals of the meeting is to enable integration of research areas, research expertise, and research resources for the purpose of optimizing scientific discovery and its translation to efficacious therapies for AD.

Outcome: The general program will be followed by a writing session during which a select group of experts together with NIA/NIH staff and representatives from other US AD-funding agencies and NAPA Council members will formulate recommendations which will inform research priorities and serve as the basis for updating and refining the NAPA research milestones for measuring progress towards the goal to prevent or treat AD by 2025.

ALZHEIMER’S DISEASE RESEARCH SUMMIT 2015: PATH TO TREATMENT AND PREVENTION

TABLE OF CONTENTS

Agenda 2

Participant Biographies 8

Recommendations from the NIH AD Research Summit 2012 25

NIA/NIH Funding Initiatives Developed in Response to the Recommendations from the NIH AD Research Summit 2012 30

Lunch Options 32

Video, Photography, Social Media Disclosure 32

2

ALZHEIMER’S DISEASE RESEARCH SUMMIT 2015: PATH TO TREATMENT AND PREVENTION

Natcher Auditorium, NIH CampusBethesda, MD

February 9–10, 2015

DAY ONE: FEBRUARY 9, 20157:00 a.m.–8:00 a.m. Registration

8:00 a.m.–8:15 a.m. Introductory Remarks Francis Collins (NIH Director)

8:15 a.m.–8:30 a.m. NAPA Research Milestones: Process and Progress Richard Hodes (NIA Director)

8:30 a.m.–9:30 a.m. Plenary Lectures

Socioeconomic Burden of AD: Update on National and International Trends

Kenneth Langa (University of Michigan)

Socioeconomic Burden of AD: Update on Global Trends with a Focus on Developing and Under-Developed Countries: Implications for Research

Martin Prince (King’s College London)

Deconstructing the Complexity of AD David Bennett (Rush University)

9:30 a.m.–11:45 a.m. Session I: Interdisciplinary Research to Understand the Heterogeneity and Multifactorial Etiology of Alzheimer’s Disease

The transformation of biology into a data-intensive science and the availability of large scale molecular, clinic-pathologic, phenotypic, and other types of relevant patient data offer unprecedented opportunities for understanding the complexity of the disease process and advancing diagnostics and treatments and bring unique challenges related to data sharing and integration. This session will address:

• key research questions related to understanding the complex biology of AD such as the role of cerebral microvasculature and inflammation

• approaches, tools and technologies needed to identify and quantify the variety of disease trajectories and phenotypes of risk and to translate genetic and epidemiological information into mechanistic insight

• issues related to harnessing the power of Big Data and ensuring the transparency, reproducibility and translatability of basic research

Chairs: Kelly Bales (Pfizer) Roberta Diaz Brinton (University of Southern California)

3

Speakers: 9:30 a.m.–10:20 a.m. Roberta Diaz Brinton (University of Southern California) Understanding Bioenergetic Compromise and Gender-Related Phenotypes of

AD Risk

Philip De Jager (Broad Institute of MIT and Harvard) Integrative Approaches to Understand Inflammatory Mechanisms of AD

Berislav Zlokovic (Keck School of Medicine at USC) Role of Microvasculature in AD and Related Dementias

Panelists: 10:20 a.m.–10:55 a.m. Bradley Hyman (Harvard University) Gerard Schellenberg (University of Pennsylvania) Joel Dudley (Icahn School of Medicine at Mount Sinai) Gareth Howell (Jackson Labs) Li-Huei Tsai (MIT) Lawrence Goldstein (University of California, San Diego) Kelly Bales (Pfizer)

Moderated Discussion: 10:55 a.m.–11:45 a.m.

LUNCH: 11:45 A.M.–12:45 P.M.12:45 p.m.–3:00 p.m. Session II: Transforming AD Therapy Development: From Targets to Trials

We are in the midst of a transformation of the linear, target-based drug development paradigm into one with a network centric view of targets and drug-target integrations. This session will feature new approaches to target and biomarker discovery for AD as well as clinical trial design and highlight examples of successful use of systems-based, data-driven approaches to drug repositioning and combination therapy development for other complex diseases. Additional topics of discussion will include:

• development of pharmacodynamic animal models for use in preclinical therapy development

• use of computational approaches for PK/PD modeling

• multi-sector collaborations for data sharing to enable comprehensive success/failure analysis in preclinical and clinical drug development

Chairs: Eric Schadt (Icahn School of Medicine at Mount Sinai) Samantha Budd Haeberlein (Biogen Idec)

Speakers: 12:45 p.m.–1:35 p.m. Reisa Sperling (Harvard University) Current and Emerging Trends in Clinical Development for AD

Julie Stone (Merck) Quantitative Systems Pharmacology Approaches to Understand Drug-

Drug Target Interactions

Eric Schadt (Icahn School of Medicine at Mount Sinai) Transforming Target and Biomarker Discovery for AD Using Network

Biology Approaches

4

Panelists: 1:35 p.m.–2:10 p.m. Joel Dudley (Icahn School of Medicine at Mount Sinai) Daniel Cohen (Pharnext) Hugo Geerts (In Silico Biosciences) Rima Kaddurah-Daouk (Duke University) Barry Greenberg (Toronto Dementia Research Alliance) Eric Reiman (Banner Institute) Samantha Budd Haeberlein (Biogen Idec)

Moderated Discussion: 2:10 p.m.–3:00 p.m.

3:00 p.m.–5:15 p.m. Session III: New Strategies for Prevention

Reducing the risk and/or delaying disease onset will have tremendous impact on the socioeconomic burden of AD. Central to achieving this goal is gaining an in-depth understanding of the mechanisms of cognitive resilience despite the presence of multiple pathologies, identifying critical windows of vulnerability and quantifying predictors of long-term brain health. This session will review our current understanding of disease progression and feature advances in genetics, epigenetics, epidemiology, and cognitive/behavioral sciences that can inform the development of prevention strategies (pharmacological and non-pharmacological). Major topics of discussion will include:

• understanding mechanisms of vascular and metabolic risk to develop effective prevention strategies

• understanding the complex interaction between genes and environment as it relates to AD risk

• developing innovative trial designs for disease prevention in community based cohort studies

• advancing the science of behavior change to ensure that effective prevention strategies are successfully implemented in the population

Chairs: David Bennett (Rush University) Suzanne Craft (Wake Forest Medical School)

Speakers: 3:00 p.m.–3:50 p.m. Chirag Patel (Harvard University) Data Driven Approaches to Interrogate Gene-Environment Interactions for

Complex Diseases

Jonathan Mill (University of Exeter and King’s College London) Epigenomics of AD: Implications for Disease Prevention

Monique Breteler (DZNE) Leveraging Knowledge of Vascular Risk Factors for AD Prevention

Panelists: 3:50 p.m.–4:30 p.m. Alison Goate (Icahn School of Medicine at Mount Sinai) John “Keoni” Kauwe (Brigham Young University) Claes Wahlestedt (University of Miami) Suzanne Craft (Wake Forest School of Medicine) David Holtzman (Washington University at St Louis) Raj Shah (Rush University) Lenore Launer (NIA/NIH) Abby King (Stanford University)

Moderated Discussion: 4:30 p.m.–5:15 p.m.

5

DAY TWO: FEBRUARY 10, 20157:30 a.m.–8:00 a.m. REGISTRATION

8:00 a.m.–10:00 a.m. Session IV: Innovating Disease Monitoring, Assessment, and Care

Advances in information technology and mHealth offer unprecedented opportunities to improve our ability to monitor the well-being of patients across multiple dimensions in real time. The availability of these data is critical to optimize and customize the delivery of care. This session will discuss:

• the needs and opportunities to innovate disease monitoring and disease assessment

• research gaps in integrating care

• technologies that enable in-place monitoring of individuals at all stages of the disease and integrating this information with other patient-relevant data in order to refine our understanding of disease progression and our ability to build predictive models of disease

• technologies that will help alleviate the burden of care

Chairs: Christopher Callahan (Indiana University) Wendy Nilsen (NIH OBSSR)

Speakers: 8:00 a.m.–8:50 a.m. Wendy Nilsen (NIH OBSSR and NSF Smart and Connected Health) mHealth Approaches for Disease Monitoring and Care

Jeffrey Kaye (Oregon Health and Science University) Innovative Technologies for Disease Monitoring in AD

Laura Gitlin (Johns Hopkins University) Research Gaps in Integrating Care for AD

Panelists: 8:50 a.m.–9:25 a.m. Jennifer Manly (Columbia University) Paul Maruff (Cog State) Rhoda Au (Boston University) Max Little (Wellcome Trust/MIT) Nancy Vuckovic (Intel) Christopher Callahan (Indiana University)

Moderated Discussion: 9:25 a.m.–10:00 a.m.

10:00 a.m.–12:00 p.m. Session V: Empowering Patients, Engaging Citizens

The acceleration of the process of discovery, development and delivery of critically needed treatment and prevention for AD in large part depends on patient/citizen awareness and engagement. This session will focus on:

• issues of recruitment

• health disparities

• patient/citizen participation in innovating patient consent, data sharing and trial design

• the emergence of Citizen Science as a collaborative approach that enables citizens to more actively participate in the full spectrum of scientific research

6

Chairs: Sharon Terry (Genetic Alliance) Reisa Sperling (Harvard University)

Speakers: 10:00 a.m.–10:50 a.m. Sharon Terry (Genetic Alliance) The Role of Patients in Transforming Drug Development

John Wilbanks (Sage Bionetworks) Citizen Participation in Innovating Informed Consent, Data Sharing and Trial Design

Sally Okun (Patients Like Me) Direct Engagement of Patients in Research

Panelists: 10:50 a.m.–11:20 a.m. Meryl Comer (Geoffrey Beene Foundation) Stephanie Monroe (African American Network Against Alzheimer’s) Constantina Mizis (The Latino Alzheimer’s & Memory Disorders Alliance) Lisa Barnes (Rush University) Pietro Michelucci (Human Computation Institute) Jennifer Couch (NCI/NIH)

Moderated Discussion: 11:20 a.m.–12:00 p.m.

LUNCH 12:00 P.M.–1:15 P.M.1:15 p.m.–3:20 p.m. Session VI: Enabling Partnerships for Open Innovation

This session will feature a number of transformative programs and public private partnerships (US and international) promoting the open source ethos in biomedical research and drug development and discuss how these can be used to accelerate AD therapy development. Highlighted programs and partnerships will include: the NIH Big Data to Knowledge Program (BD2K), BRAIN and the Accelerating Medicines Partnership-AD program.

Chairs: Stephen Friend (Sage Bionetworks) Peter Lansbury (Lysosomal Therapeutics/Harvard University)

Speakers: 1:15 p.m–1:50 p.m. Philip Bourne (NIH Office of Data Science) NIH BD2K Program: Harnessing the Power of Big Data in Biomedical Research

Stephen Friend (Sage Bionetworks) Creating a Knowledge Network to Enable Precision Medicine for AD

7

Panelists: 1:50 p.m.–2:35 p.m. Thomas Insel (NIMH/NIH) Neil Buckholtz (NIA/NIH) Tetsuyuki Maruyama (Takeda) Simon Lovestone (University of Oxford) Antony Williams (Royal Society of Chemistry) Diane Stephenson (Coalition Against Major Diseases) Diana Shineman (Alzheimer’s Drug Discovery Foundation) Maria Carrillo (Alzheimer’s Association) Peter Lansbury (Lysosomal Therapeutics/Harvard University)

Moderated Discussion: 2:35 p.m.–3:20 p.m.

3:20 p.m.–3:50 p.m. Presentation by Dennis Gillings (World Dementia Envoy)

GENERAL PROGRAM ENDS

8

ALZHEIMER’S DISEASE RESEARCH SUMMIT 2015: PATH TO TREATMENT AND PREVENTION

Participant Biographies

RHODA AU, PHD

Dr. Au is Professor of Neurology at Boston University School of Medicine and Senior Investigator/Director of Neuropsychology at the Framingham Heart Study. Since1990, she has helped oversee daily operations of their multi-generation project on imaging, genetic, biomarker and cognitive precursors of neurological disorders. Her primary research focus is cognitive aging, particularly for preclinical neuropsychological indicators of risk for disease.

She also has an MBA and is developing a translational innovation program with Chinese institutions focused on a joint Aging Well Initiative that includes development of a Chinese national cohort study and new technologies to advance ground-breaking research.

KELLY R. BALES, PHD

Dr. Bales obtained her PhD from Indiana University and currently leads a group of scientists focused on mechanisms and targets implicated in the pathophysiology of neurodegenerative diseases. She has more than 20 years experience in the pharmaceutical industry and has led several projects from mechanism identification to “first in human studies.” Additionally, she and her laboratory have made seminal contributions

investigating the interaction between apolipoprotein E and β-amyloid. Dr. Bales is recognized internationally as an expert in the area of pre-clinical animal models of Alzheimer’s disease, has co-authored more than 80 peer-reviewed publications, numerous review articles and invited book chapters. She is also co-inventor on numerous patents related to novel therapies for AD.

LISA L. BARNES, PHD

Dr. Barnes is the Director of the Rush Center of Excellence on Disparities in HIV and Aging in the Rush Alzheimer’s Disease Center, and a professor in the departments of Neurological Sciences and Behavioral Sciences at Rush University Medical Center. She earned a PhD in biopsychology from the University of Michigan and a postdoctoral fellowship in cognitive neuroscience from the University of California, Davis. She is the Principal Investigator for a

number of community-based cohort studies and has been involved with several investigator-initiated NIH funded studies that focus on race, health disparities and aging.

9

DAVID A. BENNETT, MD

Dr. Bennett is Director of the Rush Alzheimer’s Disease Center and the Robert C. Borwell Professor of Neurological Sciences at Rush University Medical Center in Chicago. The Rush Alzheimer’s Disease Center is a free-standing multidisciplinary research and clinical center that studies a wide range of common chronic conditions of aging, including Alzheimer’s disease, stroke, Parkinson’s disease, sleep and circadian biology, HIV, immune function,

gait disorders, neuro- and behavior economics, decision making and well-being. He is principal investigator of several studies funded by the National Institute on Aging including the Religious Orders Study and the Rush Memory and Aging Project. His studies incorporate imaging, omics, medical devices, biospecimens including post-mortem brain, spinal cord, nerve and muscle into community-based cohort studies of aging and disease. He is also principal investigator of two grants funded by NIH through the Accelerating Medicines Partnership to identify novel therapeutics for Alzheimer’s disease. He serves on numerous international advisory and editorial boards. He has more than 500 peer-reviewed manuscript publications.

PHILIP E. BOURNE, PHD

Dr. Bourne is the Associate Director for Data Science (ADDS) at the National Institutes of Health. Formerly, he was Associate Vice Chancellor for Innovation and Industry Alliances, a Professor in the Department of Pharmacology and Skaggs School of Pharmacy and Pharmaceutical Sciences at the University of California San Diego, Associate Director of the RCSB Protein Data Bank and an Adjunct Professor at the Sanford Burnham Institute.

He serves the national biomedical community through contributing ways to maximize the value (and hence accessibility) of scientific data. His research focuses on relevant biological and educational outcomes derived from computation and scholarly communication. He has published over 300 papers and 5 books, one of which sold over 150,000 copies. Dr. Bourne is a Past President of the International Society for Computational Biology, an elected fellow of the American Association for the Advancement of Science (AAAS), the International Society for Computational Biology (ISCB) and the American Medical Informatics Association (AMIA).

MONIQUE M.B. BRETELER, MD, PHD

Dr. Breteler is the Director of Population Health Sciences at the German Center for Neurodegenerative Diseases (DZNE) in Bonn. Prof. Breteler’s research focuses on the etiology and preclinical detection of neurodegenerative and cerebrovascular diseases. She was one of the first epidemiologists to challenge the strict clinical distinction between Alzheimer’s disease and vascular dementia, and to incorporate brain imaging

into population based studies. In Bonn, she is currently establishing the Rhineland Study, a prospective cohort study of 30,000 individuals aiming to identify causes and preclinical multimodal biomarker profiles of neurodegenerative and neuropsychiatric diseases.

10

ROBERTA DIAZ BRINTON, PHD

Dr. Brinton is the Vanderveen Chair in Therapeutic Discovery and Development at the University of Southern California, where she is Professor of Pharmacology and Pharmaceutical Sciences, Biomedical Engineering, and Neurology. She received her PhD from the University of Arizona and conducted postdoctoral research at Rockefeller University. She leads NIA sponsored basic, translational and clinical research focused on

elucidating mechanisms underlying late onset Alzheimer’s disease, with emphasis on the aging female brain. Her discovery and translational research has led to development of systems biology therapeutics currently in clinical trials that target the bioenergetic and regenerative systems of the female and male brain to prevent, delay and treat Alzheimer’s.

NEIL S. BUCKHOLTZ, PHD

Dr. Buckholtz is the Director of the Division of Neuroscience (DN) at the National Institute on Aging, National Institutes of Health (NIH), Bethesda, Maryland. The DN supports extramural research to understand the neural and behavioral processes associated with the aging brain. A major focus of DN is the support of basic, clinical and epidemiological studies of Alzheimer’s disease. Dr. Buckholtz holds a doctorate in physiological psychology

from the University of Wisconsin, Madison and was a faculty member at the Medical University of South Carolina, Department of Psychiatry, from 1970-1983, before coming to NIH.

SAMANTHA BUDD HAEBERLEIN, PHD

Dr. Budd recently joined Biogen Idec in the role of Vice President for Pain, Orphan Neurology, Ophthalmology, and early Alzheimer’s in the Clinical Development organization. Previously, she held senior R&D roles at AstraZeneca in both Sweden and the US for 14 years. She has led science teams and discovery, diagnostic and clinical development projects out to Ph3. She has seen more than 20 candidate drugs through

preclinical testing, and many of these into clinical testing. Passionate about using biomarkers to make decisions in early clinical development, in 2010 Dr. Budd built and headed the first Translational Science function at AstraZeneca. She has a BSc and PhD in Biochemistry from the University of Dundee in Scotland and has conducted research at the Neurosurgery Department, Brigham & Women’s Hospital, Harvard Medical School in Boston, and The Center for Neuroscience Research at The Burnham Institute in San Diego.

CHRISTOPHER M. CALLAHAN, MD

Dr. Callahan is the Cornelius and Yvonne Pettinga Professor in Aging Research, a scientist in the Regenstrief Institute, Inc., and Director of the Indiana University Center for Aging Research. Dr. Callahan’s research activities and clinical practice focus on older adults with dementia and depression as well as the impact of multi-morbidity on the aging brain. Over the past 25 years, this work has been supported by the NIA, the NIMH, the AHRQ, the John

A. Hartford Foundation, and the Indianapolis community.

11

MARIA C. CARRILLO, PHD

Dr. Carrillo is a Vice President, Medical and Scientific Affairs, at the Alzheimer’s Association, where she has a wide range of responsibilities, including oversight of the Association’s granting process and communication of scientific findings within and outside of the organization. Dr. Carrillo is responsible for overseeing the International Research Grant Program, the mechanism through which the Association funds research. In addition

to ensuring the smooth review of applications and distribution of awards to successful applicants, she is responsible for sharing results and ongoing investigations with a wide range of constituents. Dr. Carrillo also manages several Association initiatives. One of these is the Alzheimer’s Association Research Roundtable, which provides a forum for pharmaceutical companies to discuss trends in Alzheimer’s research and therapeutic targets. Other Association programs managed by Dr. Carrillo include the World-Wide Alzheimer’s Disease Neuroimaging Initiative (WW-ADNI), which is a multi-country research effort aimed at finding biomarkers for early detection of Alzheimer’s and the Working Group on Technology (WGT), which aims to promote the use of technologies available today for the support of individuals affected by Alzheimer’s disease to retain their independence as long as possible. Dr. Carrillo is a member of the Genworth Financial Medical Advisory Board and an Advisory Committee member for The Shriver Report.

DANIEL COHEN, MD, PHD

Dr. Cohen is a leading expert and pioneer in the field of genomics, pharmacogenomics and combination medicine. He is currently the CEO and Chairman of Pharnext, a French biotech company applying network pharmacology approaches to develop combinations of repositioned drugs for the treatment of severe unmet neurological needs. Pharnext’s clinical pipeline focuses on Charcot-Marie-Tooth, Alzheimer’s and Parkinson’s disease. Dr.

Cohen is a professor of medical genetics at the University of Paris and the co-founder of the Center for the Study of Human Polymorphisms (CEHP), an international genetics research center located in Paris, Genethon and Millennium Pharmaceuticals. He is a recipient of numerous awards including the Legion of Honor and the American Academy of Achievement’s Golden Plate Award.

MERYL COMER

Meryl Comer is president and CEO of the Geoffrey Beene Foundation Alzheimer’s Initiative, which promotes early diagnosis, global innovation challenges, mhealth technology solutions and national public service campaigns like Geoffrey Beene’s Rock Stars of Science™. A co-founder of WomenAgainstAlzheimer’s, Comer is the recipient of the 2014 Wertheim Global Medical Leadership Award, 2007 Proxmire Award and 2005 Shriver

Profiles in Dignity Award. In 2012, she led the formation of the 21st Century BrainTrust® (21CBT), a non-profit partnership to advance mobile health technologies and brain health. Comer has been the subject of primetime news stories by ABC’s Nightline and the PBS NewsHour with Jim Lehrer. One hundred percent of proceeds from her new New York Times Bestseller book, Slow Dancing with a Stranger, will support Alzheimer’s research.

12

JENNIFER COUCH, PHD

Dr. Couch is the Chief of the Structural Biology and Molecular Applications Branch, Division of Cancer Biology, NCI, NIH. Dr. Couch’s branch supports research and development of enabling technologies, models and methodologies including structural biology and biophysical characterization; bioinformatics, computational biology, mathematical modeling, data science, systems biology, citizen science and crowdsourcing methods; and

bioengineering, biomimetics and biotechnology. Dr. Couch co-leads the NIH Citizen Science Working Group. She leads efforts in data analysis and software development for the NIH Big Data to Knowledge Program and the NCI Integrative Cancer Biology Program, and she participates in trans-NIH and trans-agency efforts in a variety of areas including single cell, inter-disciplinary research, systems pharmacology, and games.

SUZANNE CRAFT, PHD

Dr. Craft is Professor of Medicine and directs the Healthy Brain Aging and Alzheimer’s Prevention Program at Wake Forest University. She earned a PhD from the University of Texas and completed fellowships in neuropsychology and behavioral neuroscience at Boston University and Harvard Medical School. Her research focuses on the role of metabolic dysregulation in AD. Dr. Craft currently leads a multi-center study testing

intranasal insulin as a therapy for Alzheimer’s dementia that was funded as part of the National Plan to Address Alzheimer’s Disease. She is a recipient of an NIH MERIT Award and an Alzheimer’s Association Zenith Award, and is a member of the Alzheimer’s Association Medical and Scientific Advisory Council.

PHILIP DE JAGER, MD, PHD

Dr. De Jager is an Associate Professor of Neurology at Harvard Medical School and Director of the Program in Translational NeuroPsychiatric Genomics within the Ann Romney Center for Neurologic Diseases in the Department of Neurology at Brigham and Women’s Hospital. He is the first incumbent of the Steven R. and Kathleen P. Haley Distinguished Chair for the Neurosciences. He is a practicing clinical neuroimmunologist. The goal of Dr. De Jager’s

work as a clinician-scientist is to apply modern methods of neuroimmunology, statistical genetics and computational biology to first delineate and then intervene in the sequence of events leading from health to neurodegenerative diseases.

JOEL DUDLEY, PHD

Dr. Dudley is the Director of Biomedical Informatics at Mount Sinai School of Medicine and an Assistant Professor of Genetics and Genomic Sciences. Prior to Mount Sinai, he held positions as Co-founder and Director of Informatics at NuMedii, Inc. and Consulting Professor of Systems Medicine in the Department of Pediatrics at Stanford University School of Medicine, where he participated in leading research to incorporate genome

sequencing into clinical practice. His current research is focused towards solving key problems in genomics and precision medicine through the development and application of translational and biomedical informatics methodologies. His lab publishes in the areas of bioinformatics, genomic medicine, personal and clinical genomics, as well as drug and biomarker discovery.

13

STEPHEN H. FRIEND, MD, PHD

Dr. Friend is President of Sage Bionetworks, a non-profit organization that provides tools to empower citizens to contribute both their data and expertise as they see fit. He and his team developed an open-source technology platform, called Synapse, for data-intensive analysis, sharing and reuse, enabling researchers to perform cutting edge computational biology and research. He is engaging the community to crowd-source solutions to

complex biomedical questions through targeted DREAM challenges. He previously led Merck & Co’s Basic Cancer Research efforts. He co-founded and co-led the FHCRC’s “Seattle Project” and later co-founded Rosetta Inpharmatics.

HUGO GEERTS, PHD

Dr. Geerts is currently on the faculty of the University of Pennsylvania and CSO of In Silico Biosciences, a company that provides mechanistic disease modeling services in CNS drug discovery and development. After receiving a physics degree, a biophysics PhD and a bachelor’s degree in medicine, he worked with Dr. Paul Janssen at the Janssen Research Foundation (part of J&J) heading the AD tau pathology research and supported

galantamine’s clinical development. He is passionate about better translational modeling and simulation along the R&D process to reduce the failure rate of clinical trials and to get better drugs faster to the right patients.

DENNIS GILLINGS, CBE, PHD

Dr. Gillings was appointed as the World Dementia Envoy in February 2014. As the founder and executive chairman of Quintiles, the world’s largest provider of biopharmaceutical development and commercial outsourcing services, Dr. Gillings has more than 30 years’ experience. Prior to this, he was Professor of Biostatistics at the University of North Carolina. He also has personal experience of dementia, as his mother lived with the condition for 18

years until her death in 2013. He is passionate about harnessing innovation in cure and care, trying to prevent the condition and improving the lives of those living with dementia. Dr. Gillings, who was born and educated in the UK, was awarded a CBE in 2004 for services to the pharmaceutical industry.

LAURA N. GITLIN, PHD

Dr. Gitlin, an applied research sociologist, is professor in the Schools of Nursing and Medicine at Johns Hopkins University, and director of the Center for Innovative Care in Aging. She is nationally and internationally recognized for her research on developing, testing and implementing novel nonpharmacologic care approaches to enhance the well-being of older adults and families. She has received continuous funding from federal

agencies and private foundations for 28+ years. Dr. Gitlin has received numerous awards, most recently the 2014 M. Powell Lawton Award for significant contributions to gerontology and innovations in services and treatments.

14

ALISON GOATE, DPHIL

Dr. Goate is Professor of Neurogenetics in the Mount Sinai Department of Neuroscience and Director of the Ronald M. Loeb Center for Alzheimer’s disease at the Icahn School of Medicine at Mount Sinai. Dr. Goate has worked on the genetics of Alzheimer’s disease for the past 27 years. She is the recipient of numerous awards for her research, including the Potamkin Prize for Alzheimer’s disease research, the Alzheimer’s Association Zenith Award,

and the Senior Investigator Award from the Metropolitan Life Foundation. In 2012 she was elected a fellow of the American Association for the Advancement of Science.

LAWRENCE S. B. GOLDSTEIN, PHD

Dr. Goldstein is Distinguished Professor in the Department of Cellular and Molecular Medicine and the Department of Neurosciences at the University of California, San Diego (UCSD), School of Medicine, as well as Director of the UC San Diego Stem Cell Program, Scientific Director of the Sanford Consortium for Regenerative Medicine, and Director of the Sanford Stem Cell Clinical Center. He has served as Director of the UCSD Stem Cell

Program since 2006, Scientific Director of the Sanford Consortium for Regenerative Medicine since 2012, and Director of the Sanford Stem Cell Clinical Center beginning in 2013. His awards include a Senior Scholar Award from the Ellison Medical Foundation, an American Cancer Society Faculty Research Award, the Loeb Chair in Natural Sciences when he was at Harvard University, election to the American Academy of Arts and Sciences, and the 2009 Public Service Award from the American Society for Cell Biology.

BARRY D. GREENBERG, PHD

Dr. Greenberg has been involved in AD research and drug discovery since 1985. He has held positions internationally in the US, Sweden and Canada within the bio-pharmaceutical industry and was the leader of a project at AstraZeneca through lead optimization, involving up to 50 individuals from eight departments. Before joining University Health Network as Director, Neuroscience Drug Discovery and Development, he was Senior

Director of Pharmacology at Neurochem, responsible for the preclinical biology research program. He is also Strategy Director for the Toronto Dementia Research Alliance, a consortium involving academic research and five memory clinics at hospitals affiliated with the University of Toronto to create a citywide dementia research center.

DAVID HOLTZMAN, MD

Dr. Holtzman is Professor and Chair of Neurology at Washington University in St. Louis. His translational work has led to significant new insights into amyloid-β (Ab), apoE, and tau metabolism and Alzheimer’s disease. The work has shown how apoE influences Ab metabolism and deposition, the development of 2 innovative in vivo techniques that allow one to determine if AD drugs are hitting their target, and how sleep may influence AD bi-

directionally. His lab’s work led to the development of the anti-Ab antibody solanezumab, now in late stage human AD clinical trials. Newer work on anti-tau antibodies is also being assessed.

15

GARETH HOWELL, PHD

Dr. Howell’s lab applies genetics and genomics approaches to identify fundamental processes involved in the susceptibility, initiation and early propagation of age-related neurodegenerative diseases, focusing on Alzheimer’s disease, non-Alzheimer’s dementia and glaucoma with an emphasis on the beneficial and damaging roles of glial and neuroinflammatory processes in Alzheimer’s disease. A major aim of the lab, in

collaboration with other investigators at The Jackson Laboratory, is to combine knowledge from human genetics/genomics studies with the strengths of mouse genetics/genomics to develop new and improved mouse models for Alzheimer’s disease and make them readily available to the scientific community. In his previous work, Dr. Howell applied novel genomics and bioinformatics strategies to identify new molecular stages of glaucoma that preceded morphological changes.

BRADLEY T. HYMAN, MD, PHD

Dr. Hyman is a neurologist and a physician scientist with a clinical practice and laboratory effort devoted to neurodegenerative diseases including Alzheimer’s disease. He is the Jack Penney Professor of Neurology at Harvard Medical School and Massachusetts General Hospital, and directs the Alzheimer Disease Research Center. His laboratory focuses on translational studies, developing models of human neurodegenerative disease and

comparing them to human neuropathology, often applying advanced imaging techniques including in vivo multiphoton microscopy. He has won the Metropolitan Life Award and the Potamkin Award, is a member of the IOM, and serves on NIA Council.

THOMAS R. INSEL, MD

Dr. Insel is Director of the National Institute of Mental Health (NIMH), the component of the National Institutes of Health committed to research on mental disorders. Dr. Insel has served as Director of this agency since 2002. During his tenure, Dr. Insel has focused on the genetics of neurobiology of mental disorders as well as transforming approaches to diagnosis and treatment. Prior to serving as NIMH Director, Dr. Insel was Professor of

Psychiatry at Emory University where he was founding director of the Center for Behavioral Neuroscience and director of the Yerkes Regional Primate Center in Atlanta. Dr. Insel’s research has examined the neural basis of complex social behaviors, including maternal care and attachment. A member of the Institute of Medicine, he has received numerous national and international awards served in several leadership roles at NIH.

RIMA KADDURAH-DAOUK, PHD

Dr. Kaddurah-Daouk has been a seminal force in the development and evolution of the metabolomics field. At Duke she leads a comprehensive program for mapping metabolic defects across the spectrum of neuropsychiatric diseases. In partnership with ADNI genetic and biomarker cores and the metabolomics community, she is building a comprehensive metabolomics database for the ADNI consortium mapping pathway and network changes across the trajectory of disease and connecting central and peripheral metabolome

changes. In addition metabolomics data on ADNI subjects is being used to inform genomics data about functions of genes and genetic variants implicated in disease mechanism. The Pharmacometabolomics Research Network that Dr. Kaddurah-Daouk leads focuses on applying quantitative systems pharmacology approaches for defining mechanism of variation of response to drugs used for treatment of cardiovascular and neuropsychiatric diseases and for highlighting underlying disease heterogeneity.

16

JOHN KAUWE, PHD

Dr. Kauwe is an Associate Professor of Biology and head of the Bioinformatics program at Brigham Young University. He specializes in processing and analysis of genetic data and has published over 80 papers in this field. His research leverages novel phenotypes and approaches to characterize the genetic architecture of Alzheimer’s disease. Dr. Kauwe is the recipient of several awards, including the Poletsky Award, the New Vision Award, and the

McMillian Award, for his work in Alzheimer’s disease. Dr. Kauwe currently serves as the Scientific Lead for the SAGE AD Challenge and as a Senior Associate Editor for Alzheimer’s and Dementia.

JEFFREY KAYE, MD

Dr. Kaye is the Layton Professor of Neurology and Biomedical Engineering at Oregon Health and Science University. He is the Director of the NIA - Layton Aging and Alzheimer’s Disease Center and Director of the Oregon Center for Aging and Technology (ORCATECH), an NIA Roybal Center. He also directs the Geriatric Neurology program at the Portland Veteran’s Affairs Medical Center. His research has focused over the past two decades on the question

of why some individuals remain protected from frailty and dependency at advanced ages while others succumb at much earlier times. This work has relied on a number of approaches ranging across the fields of genetics, neuroimaging, physiology and continuous activity monitoring. He leads several longitudinal studies on aging including the ongoing Oregon Brain Aging Study, the Intelligent Systems for Detection of Aging Changes (ISAAC), and the Ambient Independence Measures for Guiding Care Transitions studies using ubiquitous, unobtrusive technologies for assessment of elders in their homes to detect changes signaling imminent functional decline.

ABBY C. KING, PHD

Dr. King is Professor of Health Research & Policy and Medicine at the Stanford School of Medicine. Recipient of the Outstanding Scientific Contributions in Health Psychology Award from the American Psychological Association, her research focuses on the development, evaluation, and translation of public health interventions to reduce chronic disease. Her government taskforce memberships include the US DHHS Secretary’s Scientific

Advisory Committee on National Health Promotion and Disease Prevention Objectives for 2020. An elected member of the Academy of Behavioral Medicine Research and Past President of the Society of Behavioral Medicine, she received AAMC honors for outstanding research targeting health inequities.

KENNETH LANGA, MD, PHD

Dr. Langa is a Professor in the Department of Internal Medicine and Institute for Social Research, a Research Scientist in the Veterans Affairs Center for Clinical Management Research, and an Associate Director of the Institute of Gerontology, all at the University of Michigan. He is also Associate Director of the Health and Retirement Study (HRS), a National Institute on Aging funded longitudinal study of 25,000 adults in the United States ( http://

hrsonline.isr.umich.edu ). Dr. Langa received an MD and PhD in Public Policy at the University of Chicago as a Fellow in the Pew Program for Medicine, Arts, and the Social Sciences. He is a board-certified General Internist and an elected member of the American Society for Clinical Investigation (ASCI). Dr. Langa’s research focuses on the epidemiology and costs of chronic disease in older adults, with an emphasis on Alzheimer’s disease and other dementias. In 2007, Dr. Langa was a Visiting Professor at the Institute of Public Health at the University of Cambridge, and in 2015 he will be a Visiting Professor at the World Health Organization.

17

PETER T. LANSBURY, JR., PHD

Dr. Lansbury is Chief Scientific Officer of Lysosomal Therapeutics, Inc. He graduated from Princeton University and received his PhD from Harvard University. After a postdoctoral fellowship at the Rockefeller University, he joined the faculty of the Department of Chemistry at MIT. He moved to the Harvard Medical School in 1996 and was promoted to Professor of Neurology in 2004. He was the director of the Morris K. Udall NIH Parkinson’s

Disease Research Center of Excellence. He founded Link Medicine and served as its Chief Scientific Officer from 2005 until its sale in 2012.

LENORE J. LAUNER, PHD

Dr. Launer is a Senior Scientist and Chief of the Neuroepidemiology Section in the Intramural Research Program at NIA. She directs a suite of prospective, community-based cohorts, which provide a virtual life-course study of risk factors and early biomarkers for, and consequences of brain aging. Specific research interests include the role of microvascular disease, cerebral changes in physiologic functioning, and cardio-vascular risk

factors as they are studied in observational cohorts and incorporated into prevention trials.

MAX LITTLE, PHD

Dr. Little began his career writing software, signal processing algorithms and music for video games, then moved on by way of a degree in mathematics to the University of Oxford. After postdoc positions in Oxford, he won a Wellcome Trust fellowship at MIT to follow up on his doctoral research work in behavioral and biomedical signal processing. He is currently an associate professor of mathematics at Aston University and a visiting

professor at MIT’s Media Lab.

SIMON LOVESTONE, PHD

Dr. Lovestone is Professor of Translational Neuroscience at Oxford University and also Lead for the NIHR Translational Research Collaboration in Dementia (a network of six Biomedical Research Units and Centres in England focused on dementia), deputy director of the Dementias Platform UK and co-cordinator of the European Medical Information Framework. He has research interests in the regulation of tau phosphorylation, dementia

therapeutics and the search for genetic and other biomarkers of Alzheimer’s disease. Underpinning all these studies is the use of informatics - clinical informatics, bioinformatics and the challenges of extracting value from very large variable datasets.

JENNIFER J. MANLY, PHD

Dr. Manly is an Associate Professor of Neuropsychology in Neurology at the G.H. Sergievsky Center and the Taub Institute for Research in Aging and Alzheimer’s Disease at Columbia University. Her research on cognitive and genetic aspects of aging and Alzheimer’s disease among African Americans and Hispanics has been funded by the National Institute on Aging and the Alzheimer’s Association. She has authored over 100 peer-reviewed

publications and 8 chapters. She serves on the US Department of Health and Human Services Advisory Council on Alzheimer’s Research, Care and Services, and is a member of the Alzheimer’s Association Medical and Scientific Research Board.

18

PAUL MARUFF, PHD

Dr. Maruff is a neuropsychologist. He is Chief Science Officer at Cogstate and developer of the Cogstate computerized test system. He is also Professor at the Florey Institute for Neuroscience and Mental Health at the University of Melbourne. He is chair of clinical panel of the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. His research is con-cerned with how cognition is used to guide clinical decision-making in Alzheimer’s disease.

TETSUYUKI MARUYAMA, PHD

Dr. Maruyama is currently Corporate Officer, General Manger and Head of the Pharmaceutical Research Division at Takeda Pharmaceutical Company, Ltd. Trained as a neuroscientist, Dr. Tetsuyuki held academic positions in the US and UK between 1989 and 2003, when he joined Merck Sharp and Dohme’s Neuroscience Research Centre in the UK. From 2005 to 2010, he was the Head of GlaxoSmithKline’s Centre for Research in Cognitive

and Neurodegenerative Disorders in Singapore before moving to Takeda, where he is responsible for global drug discovery efforts across all of Takeda’s therapeutic areas.

PIETRO MICHELUCCI, PHD

Dr. Michelucci directs the Human Computation Institute, a multidisciplinary innovation center that networks humans and machines in new ways to address wicked societal problems. He is Editor-in-Chief of the Springer Handbook of Human Computation (2013) and Founding Editor of the journal Human Computation. An Indiana University trained cognitive scientist, Dr. Michelucci has been advising federal research agencies since 2006.

He continues to build and bridge communities through cross-agency initiatives, speaking events, and workshops. Most recently, he won a CRA grant to lead a three-day visioning activity at the Wilson Center, which produced a national roadmap for Human Computation research.

JONATHAN MILL, PHD

Dr. Mill is Professor of Epigenetics at the University of Exeter Medical School and also heads the Psychiatric Epigenetics group at the Institute of Psychiatry, King’s College London. His group studies the role of epigenetic processes in complex disease, with a particular emphasis on neurodegenerative and neuropsychiatric disorders. Current areas of research include: epigenomic profiling in post-mortem brain tissue; investigating the role of

epigenetic variation in mediating phenotypic/disease discordance between genetically identical individuals; describing dynamic epigenetic processes in brain development and function; and exploring interactions between the epigenome and DNA sequence variation, with the aim of undertaking an integrated genetic-epigenetic approach to disease. More information on their work can be found at www.epigenomicslab.com.

CONSTANTINA MIZIS

Constantina Mizis, who specialized in Linguistic and Hispanic Studies, founded The Latino Alzheimer’s and Memory Disorders Alliance in 2008. She has dedicated over 20 years of service to Latino older adults and worked with national organizations on the development of programs for the Latino elderly, and is an active board member of the nation’s top health committees. Ms. Mizis’ work and commitment to excellence have earned recognition, from

the Illinois Governor’s office, Illinois Department on Aging, Chicago Tribune, LA Times, Univision, NBC, La Opinion, and Seattle Times.

19

STEPHANIE J. MONROE, JD

Stephanie Monroe is Director of the African American Network Against Alzheimer’s, whose mission is to engage African Americans and others in the fight to find a cure or effective treatment for Alzheimer’s by 2020. The African American Network is part of USAgainstAlzheimer’s, which is a national non-profit advocacy organization in Washington, DC. She brings to this issue over 25 years of service in the United States Senate and 3

years of Executive branch experience, serving most recently as Assistant Secretary for Civil Rights at the US Department of Education. She is regarded as a veteran political strategist and an expert on a variety of health and education policy issues.

WENDY NILSEN, PHD

Dr. Nilsen is a Health Scientist Administrator at the NIH Office of Behavioral and Social Sciences Research (OBSSR) and the Program Director for the Smart and Connected Health program at NSF. Her scientific focus is on the science of human behavior and behavior change, including utilizing technology to better understand and improve health, adherence, the mechanisms of behavior change and behavioral interventions

in complex patients in primary care. More specifically, her efforts in mobile and wireless health (mHealth) research include: serving as the NIH lead for the NSF/NIH Smart and Connected Health announcement, convening meetings to address methodology in mobile technology research, serving on numerous federal mHealth initiatives and leading the NIH mHealth training institutes. At NSF, she leads the Smart Health program, which targets science at the intersection between computer science, engineering, medicine and health, broadly defined.

SALLY OKUN

Sally Okun is the Vice President for Advocacy, Policy and Patient Safety at PatientsLikeMe, an online patient powered research network. She is responsible for bringing patient voice and insight to diverse advocacy and health policy discussions at the national and global level, and is the company’s liaison with government and regulatory agencies. She joined the company in 2008 as the manager of Health Data Integrity and oversaw the development of

the site’s Drug Safety and Pharmacovigilance Platform. Prior to joining PatientsLikeMe, Ms. Okun, a registered nurse, practiced in community-based palliative and end-of-life care and contributed to numerous clinical, research, and educational projects in this specialty area.

CHIRAG PATEL, PHD

Dr. Patel is a research associate at the Center for Biomedical Informatics at Harvard Medical School. His long-term research goal is to address problems in human health and disease by developing bioinformatics methods to reason over large-scale environmental exposure information spanning molecules to populations. Dr. Patel created the first “search engine” to search for environmental exposures, or the exposome, associated with disease. He is now

leading his own computational group under early investigator funding from the Pharmaceutical Research and Manufacturers of America (PhRMA) and the NIH National Institute of Environmental Health Sciences (NIEHS).

20

DR. MARTIN PRINCE

Dr. Prince is Professor of Epidemiological Psychiatry, Head of the Health Service and Population Research department, and joint-Director of the Centre for Global Mental Health, which is a joint King’s Health Partner and London School of Hygiene centre. He trained in Psychiatry at the Maudsley Hospital and in Epidemiology at the London School of Hygiene and Tropical Medicine. His work is oriented to the salience of mental and neurological

disorders to health and social policy in low and middle income countries (LMIC), with a focus on aging and dementia. He has coordinated, since 1998 the 10/66 Dementia Research Group, a network of researchers, mainly from LMIC working together to promote more good research into dementia in those regions. He led the development of the widely reported ADI World Alzheimer Reports for 2009 (prevalence and numbers), 2010 (societal cost) and 2011 (early intervention) and was a leading contributor to the WHO World Dementia Report 2012.

ERIC M. REIMAN, MD

Dr. Reiman is Executive Director of the Banner Alzheimer’s Institute, CEO of Banner Research, Professor of Psychiatry at the University of Arizona, University Professor of Neuroscience at Arizona State University, Clinical Director of Neurogenomics at the Translational Genomics Research Institute, Director of the Arizona Alzheimer’s Consortium, and a leader of the Alzheimer’s Prevention Initiative (API). His interests include brain

imaging, early detection and tracking of Alzheimer’s disease (AD), accelerated evaluation of investigational AD prevention therapies, establishment of a new national standard of dementia care for patients and families, and development of new models of collaboration in biomedical research.

ERIC SCHADT, PHD

Dr. Schadt is Director of the Icahn Institute for Genomics and Multiscale Biology and Chair of the Department of Genetics and Genomics Sciences at the Icahn School of Medicine at Mount Sinai. He is an expert on the generation and integration of very large-scale sequence variation, molecular profiling and clinical data in disease populations for constructing molecular networks that define disease states and link molecular biology to

physiology. He is known for calling for a shift in molecular biology toward a network-oriented view of living systems to complement the reductionist, single-gene approaches that currently dominate biology in order to more accurately model the complexity of biological systems. Prior to joining Mount Sinai in 2011, he held positions as Chief Scientific Officer at Pacific Biosciences and as Executive Scientific Director of Genetics at Rosetta Inpharmatics, a subsidiary of Merck & Co.

GERARD SCHELLENBERG, PHD

Dr. Schellenberg is a Professor in the Department of Pathology and Laboratory Medicine in the Perelman School of Medicine, at the University of Pennsylvania. His work focuses on the genetics of neurodegenerative disorders including Alzheimer’s disease, progressive supranuclear palsy, and different forms of frontotemporal lobar degeneration. Dr. Schellenberg is the founder of and leads the Alzheimer’s Disease Genetics Consortium

(ADGC), which is comprised of a group of investigators who are using genome-wide association analysis methods to identify Alzheimer’s disease genes. Dr. Schellenberg is participating in the Alzheimer’s Disease Sequencing Project (ADSP) that was initiated in 2012. He is a member of the steering committee and a PI on an NIA/NIH project to analyze the large-scale whole exome and whole genome sequence data being generated by this project.

21

RAJ C. SHAH, MD

Dr. Shah is an Associate Professor in Family Medicine and the Rush Alzheimer’s Disease Center at Rush University Medical Center. His main academic interest is the design and conduct of clinical intervention trials for the prevention, diagnosis, and treatment of common age-related conditions, such as Alzheimer’s disease, in order to improve disability-free longevity in diverse, older adults.

DIANA SHINEMAN, PHD

Dr. Shineman is the Director for Scientific Affairs at the Alzheimer’s Drug Discovery Foundation, where she develops and manages the Foundation’s drug discovery and development grant programs and strategic initiatives. She earned a PhD in Cell and Molecular Biology from the University of Pennsylvania working under Drs. Virginia Lee and John Trojanowski. She also worked as an Editorial Intern for the Journal of Clinical

Investigation and was an active member of the Penn Biotechnology Group. Dr. Shineman received a BA in Biology with a Nutrition concentration from Cornell University, where she was named a Howard Hughes Undergraduate Research Scholar.

REISA SPERLING, MD

Dr. Sperling is a neurologist, specializing in the early detection and treatment of Alzheimer’s disease. She is a Professor in Neurology at Harvard Medical School, Director of the Center for Alzheimer Research and Treatment at Brigham and Women’s Hospital, and Director of Neuroimaging for the Massachusetts ADRC at Massachusetts General Hospital. She is the Principal Investigator of the Harvard Aging Brain Study, funded by an NIA Program Project

grant. Dr. Sperling led the NIA-Alzheimer’s Association workgroup to develop guidelines for “Preclinical Alzheimer’s disease,” and currently serves on the NIA Council. She is the Project Leader for the ADCS Anti-Amyloid Treatment in Asymptomatic AD (A4) study—a three-year secondary prevention trial in 1000 clinically normal older individuals with PET amyloid imaging evidence of early Alzheimer’s disease pathology.

DIANE STEPHENSON, PHD

Dr. Stephenson is a neuroscientist by training with 30 years experience in academic neuroscience and drug discovery. Dr. Stephenson received her undergraduate degree at University of California and her PhD in Medical Neurobiology from Indiana University. Her research has focused on neurodegenerative diseases. In industry, she contributed to identification and validation of novel targets and biomarker discoveries for the treatment

of Alzheimer’s disease, stroke, autism and Parkinson’s disease. Dr. Stephenson joined Critical Path Institute in 2011 as Director of the Coalition Against Major Diseases (CAMD), a consortium dedicated to accelerating drug development for Alzheimer’s disease and Parkinson’s disease.

22

JULIE A. STONE, PHD

Dr. Stone joined Merck in 1995 following graduate studies in biomedical engineering at the University of Pennsylvania and postdoctoral research at Hoffmann-La Roche. At Merck, she has provided modeling and simulations, clinical pharmacokinetics and PK/PD support for a variety of programs, including 10 approved drugs. She currently directly supports osteoporosis (odanacatib) and Alzheimer’s disease (BACE) programs

and provides scientific supervision of clinical PK/PD and pharmacometrics across a wide range of discovery and development programs.

SHARON F. TERRY

Sharon Terry is President and CEO of Genetic Alliance, a network of disease advocacy and other health organizations that engages individuals, families and communities to transform health, and founding CEO of PXE International, a research advocacy organization for the genetic condition pseudoxanthoma elasticum (PXE), which affects her two adult children. Ms. Terry is a co-founder of the Genetic Alliance Registry and Biobank

and serves in leadership roles with the Accelerating Medicines Partnership, IOM Science and Policy Board, IOM Roundtable on Translating Genomic-Based Research for Health, PubMed Central National Advisory Committee, PhenX scientific advisory board, Global Alliance for Genomics and Health, and International Rare Disease Research Consortium. She also is Founding President of EspeRare Foundation, and led the coalition that was instrumental in the passage of the Genetic Information Nondiscrimination Act. She has received many recognitions, is author of 140 peer-reviewed papers, serves on several journals’ editorial boards, and is an editor of Genome.

LI-HUEI TSAI, PHD

Dr. Li-Huei Tsai was born in Taipei, Taiwan. In 1986, she began her PhD at the University of Texas Southwestern and performed a postdoctoral fellowship at the Cold Spring Harbor Laboratory and at Massachusetts General Hospital. She is the Picower Professor of Neuroscience and Director of the Picower Institute for Learning & Memory since 2009. Dr. Tsai was elected Fellow of the American Association for the Advancement of Science in

2008, Academician of Academia Sinica in Taiwan in 2008, and Member of the Institute of Medicine in 2011. Her research focuses on the elucidation of the cellular, molecular, and circuit mechanisms that regulate cognitive function, and how dysregulation of these mechanisms contributes to the development and manifestation of the pathology and symptoms of Alzheimer’s disease.

NANCY VUCKOVIC, PHD

Dr. Vuckovic is a medical anthropologist and Director of User Experience Research and Design for Intel’s Health Strategy & Solutions Group. Her research at Intel has included studies of clinical application of technology, delivery of home-based care, and the experiences of patients and family caregivers during care transitions. Dr. Vuckovic has over 20 years of experience in health research. Prior to joining Intel, she was a principal

investigator at the Kaiser Center for Health Research, where she developed and led health services research studies and clinical trials of behavior change interventions.

23

CLAES WAHLESTEDT, MD, PHD

At the University of Miami, Dr. Wahlestedt is currently Leonard M. Miller Professor and Associate Dean for Therapeutic Innovation. The author of 200+ papers with some 20,000 citations, his ongoing research projects concern epigenetics, mammalian transcriptomics, noncoding RNAs, and drug discovery. A native of Sweden, Dr. Wahlestedt obtained his MD and PhD degrees from Lund University. Dr. Wahlestedt was a founding faculty member and

director of neuroscience discovery at the Florida campus of The Scripps Research Institute. Before that he was an endowed professor and department chair at the Karolinska Institute in Stockholm. Previously in his career, he directed large drug discovery and biotechnology teams in the pharmaceutical industry for Astra-Zeneca and Pharmacia/Pfizer. In recent years he co-founded biotech companies, including CuRNA Inc., acquired by Opko Health and Epigenetix Inc.

JOHN WILBANKS

John Wilbanks is the Chief Commons Officer at Sage Bionetworks and a Senior Fellow at Faster Cures. He has worked at Harvard’s Berkman Center for Internet & Society, the World Wide Web Consortium, the US House of Representatives, and Creative Commons. He is a past affiliate of MIT’s Project on Mathematics and Computation and also started a bioinformatics company called Incellico, which is now part of Selventa. He holds a degree

in Philosophy from Tulane and studied modern letters at the Sorbonne.

ANTONY WILLIAMS, PHD

Dr. Williams is the VP of Strategic Development for the Royal Society of Chemistry and manager of the cheinformatics team for the RSC. He is also an adjunct professor at North Carolina State University and University of North Carolina, Chapel Hill. He started a hobby project to develop the ChemSpider database, one of the community’s primary online chemistry resources, which was ultimately acquired by the Royal Society of Chemistry. At

the RSC he is now involved with a number of national and international projects for delivering chemistry related data to the chemistry community. He is widely published and is known as the ChemConnector in the social networks. He has worked on the quality of chemistry content on Wikipedia, is a recipient of the Jim Gray award for eScience from Microsoft, and is focused on helping scientists understand the power of the web for encouraging crowd sourced participation and social networking in science.

24

BERISLAV ZLOKOVIC, MD, PHD

Dr. Zlokovic is Director of the Zilkha Neurogenetic Institute and Professor and Chair of the Department of Physiology and Biophysics at the University of Southern California, Keck School of Medicine, Los Angeles. Zlokovic has a long standing interest in understanding the role of small cerebral blood vessels, CNS microcirculation and blood-brain barrier (BBB) in the pathogenesis of neurological disorders such as Alzheimer’s disease (AD) and

related disorders, and ischemic injury as foundations for development of new therapies for AD, related neurodegenerative disorders and stroke. Using animal models and studying human brain, his laboratory has shown that damage to the BBB and brain microcirculation leads to progressive neuronal dysfunction, injury and loss. His research team has identified the cellular and molecular mechanisms in small cerebral blood vessels (genes, receptors) contributing to neuronal injury, degeneration and Alzheimer’s Abeta accumulation. His team also discovered that pericytes control key neurovascular functions (i.e., BBB integrity, blood flow) necessary for proper neuronal structure and function, and that APOE4, the major genetic risk factor for Alzheimer’s, disrupts cerebrovascular integrity causing neurodegeneration and Abeta accumulation. More recently, they developed a new BBB imaging assay in the living human brain. His preclinical studies in stroke with APC have been translated to Phase 2 trial in stroke patients.

25

ALZHEIMER’S DISEASE RESEARCH SUMMIT 2015: PATH TO TREATMENT AND PREVENTION

Recommendations from the NIH AD Research Summit 2012

Overarching Recommendations:

• Recognize the heterogeneity and the multifactorial nature of the disease.

• Employ new research paradigms such as systems biology and network pharmacology.

• Enable rapid and extensive sharing of data, disease models, and biological specimens.

• Build new multidisciplinary translational teams and create virtual and real spaces where these teams can operate.

• Develop strategies to overcome intellectual property barriers to Alzheimer’s disease drug development.

• Develop new public-private partnerships.

• Establish a National Institutional Review Board (IRB) for Alzheimer’s disease clinical research.

Session 1: Interdisciplinary Approach to Discovering and Validating the Next Generation of Therapeutic Targets for Alzheimer’s Disease

A. Intensify scientific efforts to deepen the understanding of the complex pathobiology of Alzheimer’s disease, and diversify target identification to better address the multifactorial nature of the disease. These efforts should include the use of systems biology approaches and tools, as well as cutting-edge stem cell technology.

B. Develop a better systems-level understanding of how the many discoveries that have already been made (e.g., genetic, pathological, biochemical, radiological, neuropsychological) and the contributory factors that have already been identified (e.g., Aβ, tau, apoE4, a-synuclein, TDP-43, aging, proteostasis failure, mediators of inflammation, comorbidities) are related mechanistically.

C. Facilitate the conversion of existing genetic information into mechanistic insights and therapeutic advances and continue to generate new genetic data using exome and genomic sequencing approaches to identify rare genetic variants of large functional effect.

D. Generate new experimental models (e.g., different animal species, human induced pluripotent stem [iPS] cells, in silico models) that better simulate the multifactorial etiology of Alzheimer’s disease and use these models to identify modulators of disease pathways and to assess combination treatments which may be required to defeat this disease. Ensure that these new tools and models are freely shared.

E. Develop in vivo imaging agents (tracers for PET scans) to assess target engagement and the burden of brain pathology to enable successful drug development for existing and new therapeutic targets.

F. Develop robust biomarkers that can feasibly be obtained in large cohorts of volunteers, including metabolic signatures to develop and validate diagnostic, prognostic, and surrogate biomarkers for Alzheimer’s disease and biomarkers for disease subtypes.

26

G. Establish links among peripheral biochemical changes (e.g. blood-based markers) and imaging and cerebrospinal fluid changes to identify and validate peripheral biomarkers of disease.

H. Enable rapid sharing of new data via web-based resources with the capacity to store large and diverse datasets (such as data about clinical phenotypes, genetics, epigenetics, proteomics, and metabolomics) that can be used for testing different models or hypotheses at the computational level.

I. Enable analysis of new data before publication, using approaches such as collaborative challenges open to all citizens and scientists.

J. Maximize the use of existing infrastructure and resources (e.g., research centers, biobanks, and repositories) by publicizing their availability to researchers.

K. Facilitate the creation of new translational teams to expedite the discovery and validation of new therapeutic targets. These teams should include epidemiologists, basic research scientists, geneticists, computational biologists, medicinal chemists, pharmacologists, toxicologists, pharmacogenomics experts, clinicians, and project managers, collaborating within and across institutions.

Session 2: Challenges in Preclinical Therapy Development

A. Develop infrastructure and resources to increase the likelihood that preclinical therapeutic development efforts for Alzheimer’s disease will translate to success in the clinic by:

• Creating expert advisory committees for all aspects of preclinical and early clinical drug development to assist academic drug discovery efforts

• Establishing a network of Alzheimer’s disease preclinical therapy centers integrated with existing and proposed translational infrastructure and resources (e.g., Alzheimer’s Disease Neuroimaging Initiative, Alzheimer’s Disease Centers)

• Establishing an open-access resource for reviewing and publishing negative and discrepant data.

B. Develop broad capabilities in quantitative and systems pharmacology to understand the impact of drugs on organisms, to predict dosing, to reduce toxicity, and to facilitate drug repurposing and the identification of combination therapies. This will require a wide collaboration among NIH Institutes, government, academia, industry, voluntary health organizations, and foundations including the establishment of new training programs.

C. Increase the predictive power of preclinical testing in animal models by:

• Establishing a standardized and rigorous process for the development and characterization of animal models, and ensuring their maximal and rapid availability to all researchers for preclinical drug development

• Aligning the pathophysiological features of Alzheimer’s disease animal models with the corresponding stages of clinical disease using translatable biomarkers

• Establishing guidelines for rigorous preclinical testing in animal models and reporting of both positive and negative findings.

D. Provide an expedited review track for applications focused on drug discovery, preclinical, and clinical drug development for Alzheimer’s disease to mitigate difficulties with intellectual property and commercialization issues that are imposed by the current lengthy review/grant cycle at the NIH. Establish multi-disciplinary review panels with adequate expertise to evaluate all aspects of translational research.

27

Session 3: Who to Treat, When to Treat, and What Outcomes to Measure

A. Initiate treatment trials in asymptomatic, at-risk individuals (e.g., individuals at risk genetically, older adults positive for biomarkers for Alzheimer’s disease) using uniform biomarkers and cognitive outcomes, informed by data from Alzheimer’s disease trials using patients with more advanced disease.

B. Collect DNA and other biosamples from these studies to enable subsequent interrogation based on treatment response and predictors of decline in the groups receiving placebo.

C. Expand large-scale registries and natural history cohorts of healthy individuals from early midlife to late-life, as well as individuals with subjective and/or objective cognitive impairment and use the data generated to inform clinical trial design. These cohorts should be population-based and should oversample underrepresented ethnic minorities and groups with lower education.

D. Develop, validate, and standardize sensitive neuropsychological and other clinical and behavioral measures to detect and track the earliest clinical manifestations of Alzheimer’s disease and to predict long-term clinical and functional outcomes. These measures should be sensitive to change and capture the variability in cognitive function that may be an important predictor of treatment response.

E. Optimize biomarkers for detecting and monitoring the progression of Alzheimer’s disease, and focus particularly on standardization. These biomarkers will be used to elucidate the temporal trajectories over the course of preclinical and prodromal Alzheimer’s disease, to assess the proximity to onset of clinical symptoms, and to predict long-term clinical response to treatment.

F. Develop treatments for patients with symptomatic Alzheimer’s disease and support proof of concept studies to validate novel targets for cognitive and neuropsychiatric symptoms across all disease stages.

G. Develop approaches to stratify and individualize treatments based on the heterogeneity of symptomatic patient populations.

H. Support broad infrastructure changes that will accelerate and improve the efficiency of prevention initiatives, including the formation of a national centralized Institutional Review Board for multi-center Alzheimer’s disease trials and the development of agreements for data sharing of de-identified data from both placebo and treatment arms via public database

Session 4: Drug Repurposing and Combination Therapy

A. Expand publicly available libraries of drugs, drug signatures, and Alzheimer’s disease tissues and publicize their availability to the Alzheimer research community. Consider including cell-type and region-specific expression differences in the brain and periphery at varying stages of Alzheimer’s disease, as different stages may require different drugs. Expression libraries from cognitively normal adults positive for amyloid imaging and CSF Alzheimer’s biomarkers and from centenarians without dementia could be used to identify Alzheimer’s disease-resistant expression signatures that correlate with specific drug signatures for prevention studies.

B. Maintain rigor in the development of repurposed drugs with respect to scientific rationale, as well as design of clinical trials. Provide adequate prior clinical trial evidence for safety in populations with or at risk for Alzheimer’s disease.

28

C. The optimal therapy for Alzheimer’s disease may involve the use of drug combination cocktails and require different composition of these cocktails at different stages of the illness. To facilitate the development of effective combination therapies, develop translational workgroups that include experts in network biology and network pharmacology.

D. Encourage the evaluation of drugs that simultaneously target multiple disease pathways (e.g., insulin, selective estrogen receptor modulators).

E. Develop translational groups across institutions that focus on specific therapy development efforts (e.g., apoE therapeutics, combinatorial therapeutic strategies, drug repurposing, neuropsychiatric symptoms).

Session 5: Nonpharmacological Interventions

A. Integrate epidemiological studies with mechanistic research to explore underlying pathways by which risk and protective factors contribute to the disease process.

B. Continue to identify the molecular mechanisms by which non-pharmacological interventions operate and employ systems biology approaches to examine brain health in relation to, and in concert with, other organ systems.

C. Initiate rigorously designed clinical trials in asymptomatic and cognitively impaired older adults to establish the effectiveness of physical exercise, cognitive training, and the combination of these interventions for Alzheimer’s disease treatment and prevention.

D. Combine nonpharmacological (e.g., behavioral, lifestyle, environmental) interventions with pharmacological treatments to maximize possible therapeutic benefit. Use epidemiologic information, mechanistic research in animal models, and network analysis to inform trial design and drug selection.

E. Develop standard outcome measures to enable data comparisons across studies. These include but are not limited to ecologically valid measures of real world function, quality of life, and physical and cognitive function.

F. Pursue the science of behavioral change for successful implementation of effective nonpharmacological interventions.

G. Invest in research to develop technologies that promote prevention and treatment trials, clinical care, caregiver support, and in-home monitoring.

29

Session 6: New Models of Public Private Partnerships

A. Promote and enable partnerships across all sectors involved in basic, translational, and clinical research to successfully implement an integrated translational research agenda.

B. Increase awareness of the importance and value of public private partnerships among federal agencies, other stakeholder organizations, and the public and engage the full spectrum of the Alzheimer’s disease community in various partnership activities for the advancement of AD therapy development.

C. Enable partnerships for:

• Data sharing (with standardized ontologies and metadata)

• Creating, validating and sharing tools for translational research (e.g., instruments and biomarkers, animal models, high-throughput screening assays, iPS cells).

• Expanding the precompetitive space using new models of public private partnerships such as the Arch2POCM partnership for target validation and also for product development partnerships.

D. Develop a National Institutional Review Board for Alzheimer’s disease studies accessible to both public and private funding research organizations.

30

ALZHEIMER’S DISEASE RESEARCH SUMMIT 2015: PATH TO TREATMENT AND PREVENTION

NIA/NIH Funding Initiatives Developed in Response to the Recommendations from the NIH AD Research Summit 2012

GENETICSNational Institute on Aging Analysis of Alzheimer’s Disease Genome Sequencing Project Data [U19] http://grants.nih.gov/grants/guide/pa-files/PAR-12-183.html

Limited Competition: Renewal of, and Revisions to, the Alzheimer’s Disease Genetics Consortium (U01) http://grants.nih.gov/grants/guide/pa-files/PAR-14-070.html

NEW DISEASE MODELS AND RESEARCH TOOLSHuman Cell Reprogramming for Aging and Alzheimer’s Disease Research (R21) http://grants.nih.gov/grants/guide/rfa-files/RFA-AG-12-008.html

Human Cell Reprogramming for Functional Genetics of Alzheimer’s Disease (R01) http://grants.nih.gov/grants/guide/rfa-files/RFA-AG-14-012.html

Optogenetic Tools for the Study of Neural Systems in Aging and Alzheimer’s Disease (R01) http://grants.nih.gov/grants/guide/rfa-files/RFA-AG-14-002.html

BIOLOGY OF DISEASE AND DISCOVERY OF NOVEL THERAPEUTIC TARGETSInterdisciplinary Approach to the Identification and Validation of Novel Therapeutic Targets for Alzheimer’s Disease (R01) http://grants.nih.gov/grants/guide/rfa-files/RFA-AG-13-013.html

Interdisciplinary Research to Understand the Vascular Etiology of Alzheimer’s Disease (R01) http://grants.nih.gov/grants/guide/rfa-files/RFA-AG-15-010.html

Immune and Inflammatory Mechanisms in Alzheimer’s Disease (R01) http://grants.nih.gov/grants/guide/rfa-files/RFA-AG-15-018.html

DRUG DISCOVERY AND PRECLINICAL DRUG DEVELOPMENTAlzheimer’s Disease Therapeutics Program (U01) http://grants.nih.gov/grants/guide/rfa-files/RFA-AG-13-014.html

31

CLINICAL DRUG DEVELOPMENTAlzheimer’s Disease Phase I Clinical Trials (R01) http://grants.nih.gov/grants/guide/rfa-files/RFA-AG-13-016.html

Alzheimer’s Disease Prevention Trials (R01) http://grants.nih.gov/grants/guide/rfa-files/RFA-AG-13-015.html

BIOMARKERSBiomarkers of Alzheimer’s Disease in Down Syndrome (R01) http://grants.nih.gov/grants/guide/rfa-files/RFA-AG-15-011.html

NEW TRANSLATIONAL CAPABILITIES AND INFRASTRUCTUREPlanning Grants for Alzheimer’s Disease Translational Centers for Predictive Drug Development (R34) http://grants.nih.gov/grants/guide/rfa-files/RFA-AG-14-017.html

NEW PARTNERSHIPAccelerating Medicines Partnership for Alzheimer’s Disease (AMP-AD) http://www.nih.gov/science/amp/alzheimers.htm

32

ALZHEIMER’S DISEASE RESEARCH SUMMIT 2015: PATH TO TREATMENT AND PREVENTION

Lunch Options

Scheduled lunch breaks

Monday, February 9: 11:45 a.m. – 12:45 p.m.

Tuesday, February 10: 12 p.m. – 1:15 p.m.

Box lunch pickup

Pre-ordered box lunches will be delivered just outside the auditorium to your right. Please have your purchase receipt available to claim your box lunch. All sales are final. The lunch lines will be organized by wrap type (Southwestern, Italian, Beef or Vegetable).

Where to eat

Food is NOT allowed in the auditorium. We have reserved Classroom E1/E2 for eating lunch; you may also eat in the dining room of the cafeteria upstairs, or in other public areas.

Other cafeterias on campus

The Summit is being held in Building 45 (circled on the map above). There is a full-service cafeteria at the top of the stairs to the left which is open from 6:30 a.m. to 2:30 p.m. Other lunch venues include the cafeterias in Building 38A and Building 12B (circled on map) which are open from 7:00 a.m. to 2:30 p.m.

Video, Photography, Social Media Disclosure

This Summit, “Alzheimer’s Disease Research Summit 2015: Path to Treatment and Prevention,” is a public meeting. The Summit proceedings are being video recorded, photographed, audio recorded, and closed captioned.

By attending this meeting, you grant permission to the National Institutes of Health (NIH) and the Foundation for the National Institutes of Health (FNIH) to record the Summit proceedings through these means and to reproduce, copy, or distribute worldwide any such audio, video, and photography for the purpose of education and information via the Internet, Intranets, print, and other media platforms.

Please be advised that the news media may attend and report from this session. Also, in this public venue, attendees are permitted to capture images and comments of speakers and meeting participants via the use of personal mobile devices, including telephones and tablets, and utilize forms of social media (Twitter, Facebook, Instagram, etc.) to disseminate these images and comments. These activities are not under NIH or FNIH control.

2015 AD RESEARCH SUMMIT SUPPORTED BY:

WITH GENEROUS SPONSORSHIP FROM:

Platinum Sponsor:

Gold Sponsors:

Sterling Silver Sponsor:

Silver Sponsors:

Biogen Idec Inc.Eisai Inc.

Merck

Special thanks to:

Alzheimer’s Drug Discovery Foundation