Presentation Abstract

Program#/Poster#: 729.22/I35
Title: EEG in mouse models of Alzheimer’s disease as a translational in vivo biomarker
Location: South Hall A
Presentation Time: Wednesday, Oct 21, 2009, 9:00 AM -10:00 AM
Authors: *S. C. LEISER1, J. CHIN1, M. R. BOWLBY1, R. PERI1, J. DUNLOP1, A. D. RANDALL1,2, M. PANGALOS1, P. REINHART1;
1Wyeth, Princeton, NJ; 2Wyeth Applied Neurophysiol. Group, Univ. of Bristol, Bristol, United Kingdom
Abstract: Alzheimer’s disease (AD) is characterized by the presence of dense-core plaques of insoluble amyloid (Aβ) peptide and neurofibrillary tangles composed of aggregates of hyperphosphorylated tau. Several transgenic mouse models that mirror aspects of AD pathology have been produced. These include the Tg2576 and PS1/APP that exhibit age-related development of amyloid plaques and PrP-MAPT that over express tau. Biochemical abnormalities in these strains have been extensively characterized and endorse the use of the models to study therapeutic treatments for AD, yet a systematic in vivo neurophysiological characterization is still emerging. Pathological changes in the AD brain are accompanied by dementia and electroencephalographic (EEG) abnormalities. Thus EEG may play an important role in validating transgenic models. Here we describe EEG characteristics of three mouse models of AD as a function of age and disease progression. Our results indicate that the two lines of amyloid precursor protein (APP)-based transgenic mice (Tg2576 and PS1/APP), but not the tauopathy model (PrP-MAPT), exhibit transient epileptiform and/or aberrant excitatory activity. These are accompanied by rhythmic (power spectra) changes indicative of encephalopathies likely to contribute to the cognitive impairment known to be present in these models. Specifically, the APP transgenic mice had transient bursts of excessive synchronous neuronal activity accompanied by consistently higher dominant frequencies and greater time spent in these frequencies. Furthermore, the EEG in these mice have similar hallmarks to EEG recordings from Alzheimer’s patients and are consistent with the clinical observations that AD is associated with higher prevalence of unprovoked seizures and that AD patients have altered dominant frequencies in their EEG. Moreover, even at the earliest stages of dementia characteristic abnormalities in the EEG may precede the appearance of distinctive clinical features. This makes preclinical EEG an important translational biomarker for testing therapeutic strategies in the treatment of AD.
Disclosures:   S.C. Leiser, Wyeth, A. Employment (full or part-time); J. Chin, Wyeth, A. Employment (full or part-time); M.R. Bowlby, Wyeth, A. Employment (full or part-time); R. Peri, Wyeth, A. Employment (full or part-time); J. Dunlop, Wyeth, A. Employment (full or part-time); A.D. Randall, Wyeth, C. Other Research Support (receipt of drugs, supplies, equipment or other in-kind support); M. Pangalos, Wyeth, A. Employment (full or part-time); P. Reinhart, Wyeth, A. Employment (full or part-time).
Keyword(s): ALZHEIMER'S DISEASE
EEG
APP
[Authors]. [Abstract Title]. Program No. XXX.XX. 2009 Neuroscience Meeting Planner. Chicago, IL: Society for Neuroscience, 2009. Online.

2009 Copyright by the Society for Neuroscience all rights reserved. Permission to republish any abstract or part of any abstract in any form must be obtained in writing by SfN office prior to publication.




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