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Hot Topics e29
change, especially in rural locations, is a key issue because if all staff are not
in someway involved, then sustained and enduring change is unlikely. How-
ever, educational research shows us that human beings need regular, fre-
quent repetition of information in order to learn it, adopt and sustain
change. Post training support is essential to facilitate the sustained adoption
of new workplace care actions. This paper reports on a unique educational
component of a project funded by the Australian Government Department
of Health and Ageing under the Encouraging Best Practice in Residential
Aged Care program. The aim of the overall project is to develop implemen-
tation strategies to address behaviours of concern by creating dementia
friendly environments in seven rural residential aged care facilities in Vic-
toria, Australia. This presentation focuses on the development and imple-
mentation of ‘micro-training’ to support the translation of knowledge into
practice as part of routine work schedules. Micro-training has been specif-
ically developed to address issues of sustainability following education.
Methods: The purpose of the micro-training is to provide daily contact
with the core ideas of best practice in person-centred dementia care. De-
signed to be used in small group opportunities such as shift change/hand-
overs, micro-training is a one minute piece of video followed by
a question for the group to answer in discussion for about another minute
or two. The e-resource comprises 20 one minute video presentations, each
one a message linked to principles of person-centred dementia care to ad-
dress behaviours of concern. Results: Results indicate that even poorly re-
sourced rural residential care facilities can benefit from micro-training in
supporting the introduction of evidence-based practice. Conclusions: The
micro-training approach is a simple approach to promoting shared values
to implement and sustain best practice. The value of linking messages to
key quality and accreditation documents is important.
P4-030 ELEVATED AMYLOID-BETA IMPAIRS PROTEIN
SUMOYLATION
Linda Lee, Elena Dale, Agnes Staniszewski, Hong Zhang,
Francesco Michelassi, Mikako Sakurai, Chintan Kapadia, Ottavio Arancio,
Columbia University, New York, NY, USA. Contact e-mail: ll2429@
columbia.edu.
Background: SUMOylation is a highly conserved post-translational mod-
ification in which a 11 kDa protein, SUMO (small ubiquitin-like modifier),
is covalently attached to target substrates. This modification can affect
many aspects of protein function and localization and has been recently
found to have multiple roles in neuronal physiology. Our lab has demon-
strated that SUMOylation is a novel modulator of normal synaptic plastic-
ity and memory in the hippocampus. When SUMOylation is acutely
inhibited, both ex-vivo long-term potentiation (LTP) and hippocampal-
dependent memory tasks are significantly impaired. Since synaptic and
cognitive deficits are prominent characteristics of Alzheimer’s Disease,
we have also investigated how SUMOylation may be involved in amy-
loid-beta (Ab) induced pathology. Methods: Using ex-vivo hippocampal
slice electrophysiology, we tested CA3-CA1 LTP with exposure to oligo-
meric Ab42 (200nM) while manipulating SUMOylation levels with re-
combinant transduction proteins; these constructs feature the HIV-1 TAT
domain linked to either wild-type or a dominant negative version of
Ubc9, the sole E2 SUMO ligase. Results:We initially observed that hippo-
campal slices from aged APP and APP/PS1 transgenic mice do not exhibit
increases in overall SUMOylation levels following LTP induction by theta-
burst stimulation, as is observed in control wild type slices. Following this
observation, we demonstrated next that LTP is significantly impaired to
a similar degree with either Ab42 exposure or SUMOylation knockdown
by the dominant negative Ubc9 (TAT-Ubc9dn). However, the Ab-mediated
impairment is completely rescued with concurrent application of the wild-
type Ubc9 construct (TAT-Ubc9wt). In a similar manner, hippocampal-de-
pendent memory tasks are also impaired by either Ab42 or TAT-Ubc9dn
injected into the dorsal hippocampi via cannulas. Performance in both
the Morris water maze and contextual fear conditioning is significantly
worsened with either treatment. As with the LTP experiments, enhancing
SUMOylation with TAT-Ubc9wt proteins completely rescues these Ab-
induced learning deficits. Conclusions: Our data strongly suggest that
SUMOylation is impaired under pathological elevated Ab conditions and
could be a mediating factor in the synaptic and cognitive deficits of Alz-
heimer’s Disease.
P4-031 SORCS1 ALTERS APP PROCESSING AND
VARIANTS MAY INCREASE ALZHEIMER’S
DISEASE RISK
Christiane Reitz1, Shinya Tokuhiro2, Lorraine Clark1,
Christopher Conrad1, Jean-Paul Vonsattel1, Raphael Lantigua1,
Martin Medrano3, Irene Simkin4, Jonathan Haines5, Margaret Pericak-
Vance6, Lindsay Farrer7, Joseph Lee1, Ekaterina Rogaeva2, Peter St.George-
Hyslop2, Richard Mayeux1, 1Columbia University, New York, NY, USA;2University of Toronto, Toronto, ON, Canada; 3Universidad Tecnologica de
Santiago, Santiago, Dominican Republic; 4Boston University School of
Medicine, Boston, MA, USA; 5Vanderbilt University Medical Center, Nas-
ville, TN, USA; 6University of Miami, Miami, FL, USA; 7Boston University
Schools of Medicine, Boston, MA, USA. Contact e-mail: cr2101@columbia.
edu.
Background: Sorting mechanisms that cause the amyloid precursor pro-
tein (APP) and the b- and g-secretases to colocalize in the same compart-
ment play an important role in the regulation of Ab production in
Alzheimer’s disease (AD). We and several groups have reported that ge-
netic variants in the Sortilin-related receptor (SORL1) increased the risk
of AD, that SORL1 is involved in trafficking of APP, and that under-ex-
pression of SORL1 leads to over-production of Ab. We now explored the
role of one of its homologues, the sortilin-related VPS10 domain contain-
ing receptor 1 (SORCS1), in AD. Methods: We analyzed the genetic asso-
ciations between AD and 16 SORCS1-SNPs in six independent data sets
(2809 cases and 3482 controls). In addition, we compared SORCS1 expres-
sion levels of affected and unaffected brain regions in AD and control
brains in microarray gene expression and RT-PCR sets, explored the effects
of significant SORCS1-SNPs on SORCS1 brain expression levels, and ex-
plored the effect of suppression and over expression of the common
SORCS1 isoforms on APP processing and Ab generation. Results: In-
herited variants in SORCS1 were associated with AD in all datasets
(0.001 < p < 0.049). In addition, SorCS1 influenced APP processing.
While over expression of SorCS1 reduced g-secretase activity and Ab
levels, the suppression of SorCS1 increased g-secretase processing of
APP and the levels of Ab. Conclusions: These data suggest that inherited
or acquired changes in SORCS1 expression or function may play a role in
the pathogenesis of AD.
P4-032 QUANTITATIVE AND QUALITATIVE ANALYSIS OF
INTRUSIONS, FALSE POSITIVES AND
PERSEVERATIONS IN A MEMORY TEST IN
PATIENTS WITH MEMORY COMPLAINTS
Magdalena M. Caceres, Ignacio Acuna, Jose N. Bernhardt,
Paola Premolo, Federico Scabuzzo, Sofia Tillard, Sanatorio Allende,
Cordoba, Argentina. Contact e-mail: [email protected].
Background: For the early diagnosis of Alzheimer’s disease (AD) is im-
portant to investigate potential preclinical indicators.Several studies indi-
cates the importance of characterize the errors types as well as the time
in which they appear and their specificity .Thus the cuali and cuantitative
analysis of the type of errors produced in a memory test could be useful
to identify risk population and may be used as potential screening cognitive
markers adding support to a early clinical diagnosis Methods: Thus the
present study analizes the perseverations (P), types of intrusions (I) and rec-
ognition false positive (FPr) in a test of verbal episodic memory (TAVEC
spanish) in patients who consulted for mnemonic failures. The sample
was divided into three subgroups: 17 patients with Mild Cognitive Impair-
ment subtype Amnestic (MCIa) and 50 patients without MCI, subdivided
into 27 controls without depression (C) and 23 controls with depression
(CD). Data were analyzed using descriptive statistics and nonparametric
ANOVA. Results: The results indicated that the number of false positives
discriminate MCIa group of controls, being the FP unrelated (0.015) and
the stimuls nonrelated of the B list (0.002) a strong indicator. Besides, there