Chronic mild cerebrovascular dysfunction as a cause for Alzheimer's disease? - facebook prikbord

Christian Humpel^, ^a^,

^a Laboratory of Psychiatry and Exp. Alzheimers Research, Department of Psychiatry and Psychotherapy,
Innsbruck Medical University, Austria

Received 15 July 2010;

revised 17 November 2010;

accepted 19 November 2010.

Available online 26 November 2010.

Abstract

Alzheimer's disease (AD) is a progressive chronic disorder and is characterized by ß-amyloid
plaques and angiopathy, tau pathology, neuronal cell death, and

inflammatory responses. The reasons for this disease are not known. This

review proposes the hypothesis that a chronic mild longlasting

cerebrovascular dysfunction could initiate a cascade of events leading

to AD. It is suggested that (vascular) risk factors (e.g.

hypercholesterolemia, type 2 diabetes, hyperhomocysteinemaia) causes

either damage of the cerebrovascular system including silent strokes or

causes dysregulation of beta-amyloid clearance at the blood-brain

barrier resulting in increased brain beta-amyloid. A cascade of

subsequent downstream events may lead to disturbed metabolic changes,

and neuroinflammation and tau pathology. The role of NGF on the cell

death of cholinergic neurons is discussed. Additional risk factors (e.g.

acidosis, metals) contribute to plaque development.

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T6J-51JPWS0-2&_user=10&_coverDate=11%2F26%2F2010&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=e3c90ff80f0c0fcd9dc9bbefbcd86388&searchtype=a