Statins: drugs for Alzheimer's disease?

J Neural Transm (Vienna). 2005 Aug;112(8):1057-71. doi: 10.1007/s00702-004-0273-1. Epub 2005 Jan 31.

Abstract

Evidences from cell culture experiments and animal studies suggest a strong link between cholesterol and Alzheimer's disease (AD). This relationship is supported by retrospective epidemiological studies demonstrating that statin treatment reduced the prevalence of AD in patients suffering from hypercholesterolaemia. The alternative processing of the amyloid-precursor protein (APP) in the brain of AD patients leads to the production of the neurotoxic amyloid-beta protein (Abeta), a causative factor for AD pathology. In vitro, this mechanism is modulated by alterations in cellular cholesterol levels. Moreover, lowering cholesterol in animal experiments reduced the production of Abeta in most but not all studies. These findings led to prospective clinical trials of cholesterol-lowering statins in AD patients, even if many studies do not support elevated cholesterol levels in serum and brain as a risk factor for Alzheimer's disease. Most of these studies were negative. Thus, up to date there is insufficient evidence to suggest the use of statins for treatment in patients with AD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / etiology
  • Alzheimer Disease / metabolism*
  • Amyloid beta-Peptides / biosynthesis
  • Animals
  • Brain / drug effects*
  • Brain / metabolism*
  • Brain / physiopathology
  • Cholesterol / metabolism
  • Clinical Trials as Topic
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hypercholesterolemia / complications
  • Hypercholesterolemia / drug therapy*
  • Hypercholesterolemia / physiopathology
  • Treatment Outcome

Substances

  • Amyloid beta-Peptides
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Cholesterol