| Résumé | Cerebrovascular insufficiency appears years prior to clinical symptoms in Alzheimer’s disease (AD). The soluble, highly toxic amyloid-beta (Aβ) species, generated from the amyloidogenic processing of amyloid precursor protein (APP), are known instigators of the chronic cerebrovascular hypoperfusion observed in AD patients. To date, the global response of the cerebrovascular proteome to excess soluble Aβ and to pharmacotherapy that normalizes cerebrovascular function remains poorly understood. We previously demonstrated that the anti-diabetic drug pioglitazone, currently in a Phase III trial for delay of AD onset, reverses cerebrovascular impairment in a mouse model of AD overexpressing Aβ (APP mice). In this study, we characterized the effects of soluble Aβ overproduction on the cerebrovascular proteome of mice; determined how pioglitazone-treatment affected the altered proteome; and analyzed the relationship between normalized protein levels and recovery of cerebrovascular function. |
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