Alzheimer disease--no target for statin treatment. A mini review.
Nosologically, Alzheimer disease (AD) is not a single disorder. A minority of around 400 families worldwide can be grouped as hereditary in origin, whereas the majority of all Alzheimer cases (approx. 25 million worldwide) are sporadic in origin. In the pathophysiology of the latter type, a number of susceptibility genes contribute to the disease among which are allelic abnormalities of the apolipoprotein E4 gene pointing to a link between disturbed cholesterol metabolism and sporadic AD. Cholesterol is a main component of membrane composition enriched in microdomains and is functionally linked to the proteolytic processing of amyloid precursor protein (APP). In sporadic AD, a marked diminution of both membrane phospholipids and cholesterol has been found. Evidence has been provided that high plasma cholesterol may protect from AD. In contrast to these well documented abnormalities observed in AD patients, it was assumed that an elevated cholesterol concentration might favour the generation of beta-amyloid and, thus, AD. However, a series of in vitro-and in vivo-studies did not provide evidence for the assumption that an enhanced cholesterol concentration increased betaA4-production. A harsh reduction of membrane cholesterol only caused a "beneficial" effect of APP metabolism. However, this experimentally induced condition may not be compatible to sporadic AD. The application of statins in sporadic AD did not yield results to assume that this therapeutic strategy may prevent or treat successfully sporadic AD.
Hoyer
Siegfried
S
Department of Pathology, University of Heidelberg, Im Neuenheimer Feld 220/221, D-69120 Heidelberg, Germany. siegfried.hoyer@med.uni-heidelberg.de
Riederer
Peter
P
D000375:Aging / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry / Q000502:physiology; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008566:Membranes / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016875:tau Proteins; D002784:Cholesterol