Alzheimer's disease, cholesterol, and statins: the junctions of important metabolic pathways

Angew Chem Int Ed Engl. 2013 Jan 21;52(4):1110-21. doi: 10.1002/anie.201204964. Epub 2012 Dec 20.

Abstract

Recent years have seen a significant increase in published data supporting the positive effects of statins on neurodegenerative diseases, in particular on Alzheimer's disease. Statins show neuroprotective activity by a combination of different cellular and systemic mechanisms that are based on the inhibition of the biosynthesis of cholesterol and isoprenoid by-products. The promising results obtained in vivo and in epidemiological studies are generally not in accordance with those of placebo-controlled randomized clinical trials. Nevertheless, these results make statins valuable assets for disease prevention rather than therapeutic agents for use when disease symptoms are already displayed. Thus, the modulation of midlife cholesterol and/or statin administration prior to the appearance of dementia or cognitive impairment may have a better long-term outcome.

Publication types

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

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / metabolism
  • Apolipoproteins E / metabolism
  • Cholesterol / metabolism*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Metabolic Networks and Pathways
  • Terpenes / metabolism
  • tau Proteins / chemistry
  • tau Proteins / metabolism

Substances

  • Amyloid beta-Peptides
  • Apolipoproteins E
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Terpenes
  • tau Proteins
  • Cholesterol