title: Pathophysiological Links Among Hypertension and Alzheimer's Disease.
abstract: Genetic Alzheimer's disease (AD) accounts for only few AD cases and is almost exclusively associated to increased amyloid production in the brain. Instead, the majority of patients is affected with the AD sporadic form with typical alterations of clearance mechanisms of the brain. Most studies use engineered animal models that mimic genetic AD. Since it is emerging the existence of a pathophysiological link between cardiovascular risk factors and AD etiology, the strategy to develop animal models of vascular related AD pathology could be the key toward developing novel successful therapies. On this issue, we have demonstrated that mice that have been chronically subjected to high blood pressure show deposition of amyloid aggregates, the main histological feature of AD, and loss of memory in specific tasks. More importantly, we have identified that the hypertensive challenge increases the expression of the receptor for advanced glycated end products (RAGE), leading to beta-amyloid (Aβ) deposition and learning impairment. Here, we review different murine models of hypertension, induced either pharmacologically or mechanically, leading in the long time to plaque formation in the brain parenchyma and around blood vessels. The major findings obtained till now in this particular experimental setting allow us to suggest that this appears to be a unique possibility to study the pathogenetic mechanisms of sporadic AD triggered by vascular risk factors.
authors.affiliation: Department of Angiocardioneurology and Translational Medicine, IRCCS Neuromed, Pozzilli, IS, Italy.|Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Carnevale
authors.affiliation: Department of Angiocardioneurology and Translational Medicine, IRCCS Neuromed, Pozzilli, IS, Italy.
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Perrotta
authors.affiliation: Department of Angiocardioneurology and Translational Medicine, IRCCS Neuromed, Pozzilli, IS, Italy.|Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lembo
authors.affiliation: Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy. trimarco@unina.it.
authors.forename: Bruno
authors.initials: B
authors.lastname: Trimarco
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D000818:Animals; D001522:Behavior, Animal; D001794:Blood Pressure; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D003071:Cognition; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D058225:Plaque, Amyloid; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism; D012084:Renin-Angiotensin System; D012307:Risk Factors; D015398:Signal Transduction; D013997:Time Factors
chemical_list: C000593873:Ager protein, mouse; D000067759:Receptor for Advanced Glycation End Products
keywords: Alzheimer’s disease (AD); Beta-amyloid (Aβ) deposition and cognitive impairment; Hypertension and cardiovascular risk factors; Murine models of vascular-related AD; RAGE, receptor for advanced glycated end products