Alzheimer lesions after ischemia-reperfusion brain injury.
For now the best-established and accepted theory in Alzheimer's disease (AD) etiology by most scientists is the "amyloid theory", as the main molecular factor of neurodegeneration in AD. We critically review these observations and highlight inconsistencies between the predictions of the "amyloid hypothesis" and the published data. The research of neurobiology of AD, now more than ever, needs an infusion of new concepts. Handful researchers now recognize brain ischemia as a prominent feature in AD and a potential target for therapy aimed at treatment and prevention of disease. The "ischemia-reperfusion theory" was primarily aimed at stimulating study and redirecting the focus of investigations towards ischemic cellular mechanisms of AD. To accommodate the recent progress of study in AD there is a need to synthesize all the divergent pieces of data into a coherent story. This review provides a synopsis of current information about ischemic cellular and molecular mediators involved in Alzheimer's neuropathology as well as interactions between these mediators that influence pathology. In this paper, current knowledge on the close relation between vascular disease factors and Alzheimer's type dementia will be reviewed. We will summarize the data with a special focus on Alzheimer lesions in experimental brain ischemia. Taken all together, evidence presented in this review suggests a scheme for Alzheimer's pathogenesis with ischemia playing a crucial role in influencing and linking beta-amyloid deposition to neuronal damage and clinical disease.
Pluta
Ryszard
R
Department of Neurodegenerative Disorders, Medical Research Centre, Polish Academy of Sciences, Warszawa, Poland. pluta@medres.cmdik.pan.pl
D000544:Alzheimer Disease / Q000150:complications* / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D015427:Reperfusion Injury / Q000150:complications* / Q000378:metabolism / Q000473:pathology
D016229:Amyloid beta-Peptides