Abnormal neuronal networks and seizure susceptibility in mice overexpressing the APP intracellular domain

NEUROBIOLOGY OF AGING

卷:32

Article

Vogt, D. L.¹  Thomas, D.¹  Galvan, V.^3,4  Bredesen, D. E.²  Lamb, B. T.¹  Pimplikar, S. W.¹ 

[1] Cleveland Clin, Lerner Res Inst, Dept Neurosci, Cleveland, OH 44195 USA

[2] Buck Inst Age Res, Novato, CA 94945 USA

[3] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78245 USA

[4] Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA

关键词: Alzheimer's;    AICD;    APP;    Fe65;    Electroencephalogram;    Seizure;   

DOI  :  10.1016/j.neurobiolaging.2009.09.002

来源: Elsevier

【 摘 要 】

Alterations in the processing of the amyloid precursor protein (APP) lead to familial Alzheimer's disease (AD). AD patients exhibit increased seizure susceptibility and alterations in their EEGs, which suggests that APP and its metabolites may modulate neuronal networks. Here we demonstrate that transgenic mice overexpressing APP intracellular domain (AICD) and its binding partner Fe65 exhibit abnormal spiking events and a susceptibility to induced seizures. These abnormalities are not observed in PDAPP (D664A) mice, which express high A beta levels but harbor a mutation in the APP intracellular domain. These data suggest that alterations in the levels of AICD contribute to network dysfunction in AD. (C) 2009 Elsevier Inc. All rights reserved.

【 授权许可】

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