$298 Wednesday, November 9, 2005 Poster Abstracts

Conclusion: CSF biomarkers help to detect MCI patients who develop AD.

0776 Evolution of clinical li~atmes in Dementia with Lewy-body timing long-term follow-up

Pradhan, S. Sanjay Gandhi Postgraduate Institute of Medical Sciences, Luclrnow, India.

Background: Evolution of clinical features in late stages of Dementia with Lewy-body (DLB) is not clearly known. Methods: Seven patients with features suggestive of DLB (coguitive impairment, parkinsonian features, visual hallucinations and marked fluctuation in symptoms) are described for atypical presentation during the long-term follow-up. These patients were examined at four- monthly intervals for 3-5 years and any change or development of new symptom or sign was noted. M R imaging of the brain was performed at 1-2 yr intervals. Results: After 6-18 months, marked swing in behavior from highly agitated state to a transient depressive state was noted in 5 patients; rest of the 2 had persistent psychosis. Treatment with anti-psychotic drugs was frustrating due to rapid development of extra-pyramidal syndrome. MRI showed generalized but predominantly parieto- occipital atrophy. Between 2-3 years of illness, 6 patients showed postural instability with tendency to fall forward (4 patients) or backwards (2 patients) and vertical gaze paralysis simulating PSP. Mid- brain collicular atrophy was also noted on MRI at this stage in 5 of them. Four patients were walking independently between 3-4 years and two of them had difficulty in walking tandem and limb ataxia. MRI showed additional atrophy of olives, vetmis and cerebellar hemispheres. Drop in blood pressure on standing with symptoms of postural hypotension were observed in 3 patients with 3-5 years of illness. Conclusion: Natural course of DLB needs more studies as our patients in advanced stage of the disease showed cliuical and MRI features, which may be confused with PSP or MSA.

0777 S100A9, an Inflammation-Associated Calcium-Binding Protein, Is a Binding Partner for Various Redox-Regulating Proteins in Familial Al.zheilner's Disease

Ratlimi, F x, Goyette, j2, Raftery, M 2, Shepherd, C 1, Halliday, G 1, Geczy, C 2. Z Prince of Wales Medical Research Institute and; 2 University of New South Wales, Sydney, Australia

Background: Inflammation, oxidative stress and genetic, predisposition are pathogenic factors contributing to neurodegenerative diseases including Alzheimer's disease (AD), but neuroinflammatory processes in fanfilial presenilin-1 (PS-1) AD differ from sporadic AD (S-AD). S100A9 is an inflanunation-associated protein that may regulate redox function, as suggested for S 100B. Methods: Immunohistochemistry and Western blotting assessed S100A9 expression in control and AD samples. Control, S-AD and PS-1 AD brain extracts adsorbed with anti-S100A9-inmmnoaffinity were eluted with EGTA to identify potential CaZ+-binding part- ners that were separated by SDS-PAGE and processed by mass spectrometry. Results: Like S100B, SI00A9 was consistently co-localized within neuropathological hallmarks of AD brain; soluble S100A9 was siguificantly increased in PS-1 AD. Argininase and superoxide dismutase were identified in PS-1 and S-AD extracts. Of the 7 PS-1- specific proteins, 4 can regulate redox and/or apoptosis. Caffiepsin D, which cleaves amyloid precursor protein to amyloidogenic compo- nents, was also ehited. Conclusion: The earlier onset and rapid disease progression observed in PS-1 AD cases may involve S100A9-modulated inflanmmtory and redox pathways. Further analyses and characterization of some of these are necessary.

0778 Safety of Galantanfine and Memantine in Combination Usage in the Treatment of Mild to Moderate AIzhehner's Disease

Ramaswamy, K1; Amatuiek, j2; Zhu, y2.2Jansse n Medical Aft'airs L.L.C., Titusville, New Jersey, USA; 20rtho-McNeil Neurologics, Inc., Titusville, New Jersey, USA

Background: There are no published data on the safety and tolerability of the concomitant use of galantarnine and memantine in Alzheimer's disease (AD) patients. A preliminary interim safety analysis o f an ongoing observational study of patients with mild-to-moderate AD was performed. Methods: Included in this 2-year, multi-center, prospective, open-label, observational study are patients who at entry were either receiving treatment with galantanfine (GAL) or no medication indicated for AD (untreated). Tire naturalistic design permits physicians to alter therapy as needed. Study data collected at the time of the first interim observed case (OC) analysis included patients who received memantine (MEM) as well as other treatments. Because of uneven follow-up times, the analyses were adjusted for years at risk. Results: A total of 429 subjects were analyzed in one or more groups: GAL (319), MEM (9), GAL plus MEM (148), AChEI other than GAL (other-AchEI, 18), and untreated (114). Adverse event (AE) data were compiled for a total of 259.9 patient-years at risk (y) (GAL, 158.9; MEM, 1.7; GAL-MEM 24.5; other AChEI, 4.5; untreated, 70.3). A total of 19.3% patients reported AEs (10.32 Per Year at Risk [PYR]). AEs were reported by 14.1% (10.28 PYR) of GAL, 16.7% (0.33) of GAL-MEM and by 19.1% (0.38) of untreated subjects. Furthermore, AEs were reported by 22.2"/0 (1.18) and 5.6% (10.22) of MEM and other-AChEI treated subjects, respectively. Conclusion: Preliminary data analysis suggest that GAL-MEM use may be safe and well tolerated compared to no AD treatment, in a mild to moderate AD population.

0779 CSF Tau and Amyloid J~I-42 (AJ}42) as possible Biomarkers of Alzhehner disease

Ravid, R l, Kanrphorst, W. /Tw Netherland~ Brain Bank, Amsterdam, The Netherlands

The diagnosis of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD) is severly hampered by the absence of suitable biomarkers that can be measured in body fluids such as blood and cerebrospinal fluid (CSF). These markers can explain the pathological mechanisms underlying the various diseases and have a predictive value in early diagnostics. Bio Banks are an essential repository for post-mortem specimens and body fluids The biomarkers identified in blood and CSF may reflect fluc- tuation in processes; they also indicate the formation of the extra- cellular amyloid-containing senile plaques (SP's) and intracelhilar neurofihiillar tangles (NFT's) consisting of (hyperphosphorylated) tau-proteins. It has been shown that ante-mortem CSF Amyloid [~-4~ (A[~42) is significantly decreased in AD. CSF tau, and more specifically its hyperphosphorylated forms (p-tau) is significantly higher in AD patients as compared to non-dementing age-matched controls.

Biomarkers reflect the processes that underly the pathological hallmarks of the disease. However, the defiuite and accurate diagnosis can only be validated at post-mortem autopsy.

In the coming decenia brain banks will collect, preserve and type RNA and DNA extracted from brain specimens in order to update the pathological hallmarks of AD and PD.

In the present study we show that biobanking is vital to assess the validity of ante-mortem and post-mortem CSF A[~42 and P-tau in reflecting tire hallmarks of AD to support the development of reliable early diagnostic procedures.