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Séminaire - Guisepe LemboAlzheimer Disease and Arterial Hypertension.

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 and typically has an alteration of clearance mechanisms.

The identification of factors that influence the onset and progression of sporadic AD is a key step toward understanding its mechanism(s) and developing successful therapies. Increasing epidemiological studies describe a strong association between AD and cardiovascular risk factors, particularly hypertension, that exerts detrimental effects on the cerebral circulation, favouring chronic brain hypoperfusion.

However, a clear demonstration of a pathophysiological link between cardiovascular risk factors and AD aetiology is still missing. To deepen our knowledge of the mechanisms involved in brain response to hypertension and their possible role in promoting amyloid deposition in the brain, we have deeply investigated murine models of hypertension, leading in the long time to plaque formation in the brain parenchyma and around blood vessels and cognitive deficits of learning and memory tasks.

During the seminar I will go through our major findings, obtained in this particular experimental setting that 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.

Selected publications

1.    Carnevale D, Mascio G, D'Andrea I, Fardella V, Bell RD, Branchi I, Pallante F, Zlokovic B, Yan SS, Lembo G. Hypertension induces brain β-amyloid accumulation, cognitive impairment, and memory deterioration through activation of receptor for advanced glycation end products in brain vasculature. Hypertension. 2012 Jul;60(1):188-97.

2.    Carnevale D, Lembo G. 'Alzheimer-like' pathology in a murine model of arterial hypertension. Biochem Soc Trans. 2011 Aug;39(4):939-44.

3.    Carnevale D, Mascio G, Ajmone-Cat MA, D'Andrea I, Cifelli G, Madonna M, Cocozza G, Frati A, Carullo P, Carnevale L, Alleva E, Branchi I, Lembo G, Minghetti L. Role of neuroinflammation in hypertension-induced brain amyloid pathology. Neurobiol Aging. 2012 Jan;33(1):205.e19-29.

4.    Gentile MT, Poulet R, Di Pardo A, Cifelli G, Maffei A, Vecchione C, Passarelli F, Landolfi A, Carullo P, Lembo G. Beta-amyloid deposition in brain is enhanced in mouse models of arterial hypertension. Neurobiol Aging. 2009 Feb;30(2):222-8.

5.    Poulet R, Gentile MT, Vecchione C, Distaso M, Aretini A, Fratta L, Russo G, Echart C, Maffei A, De Simoni MG, Lembo G. Acute hypertension induces oxidative stress in brain tissues. J Cereb Blood Flow Metab. 2006 Feb;26(2):253-62

Jean Luc Morel (jean-luc.morel @ u-bordeaux2.fr)

Sapienza


Agenda