889 IS RAGE THE SO FAR UNIDENTIFIED TRAIT D'UNION BETWEEN VASCULAR RISK FACTORS AND ALZHEIMER'S DISEASE? Rita Businaro1, L. Capriotti1, M. Corsi1, M. Leopizzi1, V. Nicolia2, A. Fuso2 1Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, 2Surgery 'P. Valdoni', Sapienza University of Rome, Rome, Italy Aim: The receptor for advanced glycation end products (RAGE), is considered to be a key mediator of atherogenesis. Recent findings indicate the important role played by RAGE in the progression of Alzheimer's disease (AD). It has been shown that RAGE signaling contributes to the production of proinflammatory cytokines, leading to the impairment of neuronal functions and to the amyloid accumulation. Moreover, atherosclerosis, stroke and cardiac disease in the aging individual, could result in cerebrovascular dysfunction and trigger AD pathology. It is known that diet depleted in folate and vitamins B6 and B12 promotes an enhanced expression of RAGE and leads to hyperhomocysteinemia, a well-known risk factor for the development of cardiovascular disease as well as for late onset AD. This work aims at evaluating the effects of hyperhomocysteinemia, induced by B vitamin deficiency, on RAGE expression. Methods: TgCNRD8 mice carrying a Indiana/Swedish mutated APP transgene, an animal model of AD, were grown either with control or B vitamin deficient diet. We measured RAGE by immunohistochemistry, western blots, real-time PCR. Results: B vitamin deficiency enhances RAGE expression in particular at the level of frontal and parietal microvasculature. Both neurons and endothelium in the hippocampus were stained, showing an increase in the number of positive cells as well as in the amount of reaction, compared to the animals fed with a standard diet. Conclusions: B vitamin deficiency and hyperomocysteinemia are able to modulate RAGE expression, promoting in this way atherosclerosis progression and the transport of beta Amyloid across the BBB.
IS RAGE THE SO FAR UNIDENTIFIED TRAIT D'UNION BETWEEN VASCULAR RISK FACTORS AND ALZHEIMER'S DISEASE? / Businaro, Rita; Capriotti, L; Corsi, Mariangela; Leopizzi, Martina; Nicolia, Vincenzina; Fuso, Andrea. - ELETTRONICO. - (2012), pp. 889-889. (Intervento presentato al convegno 80th EAS Congress tenutosi a Milan, Italy nel May 26-29,2012).
IS RAGE THE SO FAR UNIDENTIFIED TRAIT D'UNION BETWEEN VASCULAR RISK FACTORS AND ALZHEIMER'S DISEASE?
BUSINARO, Rita;CORSI, MARIANGELA;LEOPIZZI, MARTINA;NICOLIA, Vincenzina;FUSO, ANDREA
2012
Abstract
889 IS RAGE THE SO FAR UNIDENTIFIED TRAIT D'UNION BETWEEN VASCULAR RISK FACTORS AND ALZHEIMER'S DISEASE? Rita Businaro1, L. Capriotti1, M. Corsi1, M. Leopizzi1, V. Nicolia2, A. Fuso2 1Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, 2Surgery 'P. Valdoni', Sapienza University of Rome, Rome, Italy Aim: The receptor for advanced glycation end products (RAGE), is considered to be a key mediator of atherogenesis. Recent findings indicate the important role played by RAGE in the progression of Alzheimer's disease (AD). It has been shown that RAGE signaling contributes to the production of proinflammatory cytokines, leading to the impairment of neuronal functions and to the amyloid accumulation. Moreover, atherosclerosis, stroke and cardiac disease in the aging individual, could result in cerebrovascular dysfunction and trigger AD pathology. It is known that diet depleted in folate and vitamins B6 and B12 promotes an enhanced expression of RAGE and leads to hyperhomocysteinemia, a well-known risk factor for the development of cardiovascular disease as well as for late onset AD. This work aims at evaluating the effects of hyperhomocysteinemia, induced by B vitamin deficiency, on RAGE expression. Methods: TgCNRD8 mice carrying a Indiana/Swedish mutated APP transgene, an animal model of AD, were grown either with control or B vitamin deficient diet. We measured RAGE by immunohistochemistry, western blots, real-time PCR. Results: B vitamin deficiency enhances RAGE expression in particular at the level of frontal and parietal microvasculature. Both neurons and endothelium in the hippocampus were stained, showing an increase in the number of positive cells as well as in the amount of reaction, compared to the animals fed with a standard diet. Conclusions: B vitamin deficiency and hyperomocysteinemia are able to modulate RAGE expression, promoting in this way atherosclerosis progression and the transport of beta Amyloid across the BBB.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
