Journal Article

X11β rescues memory and long-term potentiation deficits in Alzheimer's disease APPswe Tg2576 mice

Jacqueline C. Mitchell, Belall B. Ariff, Darran M. Yates, Kwok-Fai Lau, Michael S. Perkinton, Boris Rogelj, John D. Stephenson, Christopher C.J. Miller and Declan M. McLoughlin

in Human Molecular Genetics

Volume 18, issue 23, pages 4492-4500
Published in print December 2009 | ISSN: 0964-6906
Published online September 2009 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddp408
X11β rescues memory and long-term potentiation deficits in Alzheimer's disease APPswe Tg2576 mice

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Increased production and deposition of amyloid β-protein (Aβ) are believed to be key pathogenic events in Alzheimer's disease. As such, routes for lowering cerebral Aβ levels represent potential therapeutic targets for Alzheimer's disease. X11β is a neuronal adaptor protein that binds to the intracellular domain of the amyloid precursor protein (APP). Overexpression of X11β inhibits Aβ production in a number of experimental systems. However, whether these changes to APP processing and Aβ production induced by X11β overexpression also induce beneficial effects to memory and synaptic plasticity are not known. We report here that X11β-mediated reduction in cerebral Aβ is associated with normalization of both cognition and in vivo long-term potentiation in aged APPswe Tg2576 transgenic mice that model the amyloid pathology of Alzheimer's disease. Overexpression of X11β itself has no detectable adverse effects upon mouse behaviour. These findings support the notion that modulation of X11β function represents a therapeutic target for Aβ-mediated neuronal dysfunction in Alzheimer's disease.

Journal Article.  5657 words.  Illustrated.

Subjects: Genetics and Genomics

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