Cholesterol and Alzheimer's disease: a still poorly understood correlation

IUBMB Life. 2012 Dec;64(12):931-5. doi: 10.1002/iub.1091. Epub 2012 Nov 2.

Abstract

A large amount of evidence suggests a pathogenic link between cholesterol homeostasis dysregulation and Alzheimer's disease (AD). In cell culture systems, the production of amyloid-β (Aβ) is modulated by cholesterol, and studies on animal models have consistently demonstrated that hypercholesterolemia is associated with an increased deposition of cerebral Aβ peptides. Consequently, a number of epidemiological studies have examined the effects of cholesterol-lowering drugs (i.e., statins) in the prevention and the treatment of AD. However, while retrospective studies suggested a potential benefit of statin therapy, clinical trials produced inconsistent results. Here, we summarize the main findings from in vitro and in vivo research where the correlation between cholesterol and the neurodegenerative disorder was investigated. Recognition of this correlation could be an important step forward for our understanding of AD pathogenesis and, possibly, for the development of new therapeutic strategies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / blood*
  • Alzheimer Disease / complications
  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Anticholesteremic Agents / pharmacology
  • Anticholesteremic Agents / therapeutic use
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism*
  • Cerebral Cortex / pathology
  • Cholesterol / blood*
  • Clinical Trials as Topic
  • Disease Models, Animal
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hypercholesterolemia / blood*
  • Hypercholesterolemia / complications
  • Hypercholesterolemia / drug therapy
  • Hypercholesterolemia / pathology
  • Retrospective Studies

Substances

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