National Research Council of Canada. Human Health Therapeutics
Alzheimer's disease; amyloid precursor protein mice; pioglitazone; cerebrovascular impairment
Cerebrovascular dysfunction appears prior to Aβ-plaque deposition and measurable mnemonic impairment in Alzheimer's disease (AD) patients and amyloid precursor protein (APP)-expressing transgenic mice. The soluble, highly toxic Aβ-fragment generated from the amyloidogenic processing of APP is likely the primary instigator of chronic cerebrovascular insufficiency in APP mice. We recently demonstrated that the PPAR-gamma agonist, pioglitazone, is a potent drug for reversing cerebrovascular impairment at all stages of Aβ-induced pathology in APP mice. Our aims are to (a) characterize the effect of Aβ-overproduction on the cerebrovascular proteome of APP mice; (b) determine the extent to which pioglitazone rescues the Aβ-altered cerebrovascular proteome; and (c) determine the link between protein expression rescue by pioglitazone and functional recovery in the cerebrovasculature.
Alzheimer's and Dementia8, no. 4, Supplement (July 2012): P574–P575.