Mitchell JC, Ariff BB, Yates DM, Lau KF, Perkinton MS, Rogelj B, Stephenson JD, Miller CC, McLoughlin DM., X11beta rescues memory and long-term potentiation deficits in Alzheimer's disease APPswe Tg2576 mice., Human Molecular Genetics, 18, 23, 2009, 4492-4500
Human Molecular Genetics 18 23
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
normalisation of both cognition and in vivo long-term potentiation (LTP) 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.
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