X11beta rescues memory and long-term potentiation deficits in Alzheimer's disease APPswe Tg2576 mice.
MC LOUGHLIN, DECLAN
Metadata:Show full item record
Citation: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
Increased production and deposition of amyloid ?-protein (A?) are believed to be key pathogenic events in Alzheimer?s disease. As such, routes for lowering cerebral A? levels represent potential therapeutic targets for Alzheimer?s disease. X11? is a neuronal adaptor protein that binds to the intracellular domain of the amyloid precursor protein (APP). Overexpression of X11? inhibits A? production in a number of experimental systems. However, whether these changes to APP processing and A? production induced by X11? overexpression also induce beneficial effects to memory and synaptic plasticity are not known. We report here that X11?-mediated reduction in cerebral A? 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 X11? itself has no detectable adverse effects upon mouse behaviour. These findings support the notion that modulation of X11? function represents a therapeutic target for A?-mediated neuronal dysfunction in Alzheimer?s disease.
Medical Research Council
Series/Report no:Human Molecular Genetics