Cholesterol as a causative factor in Alzheimer's disease: a debatable hypothesis
Article first published online: 2 JAN 2014
© 2013 International Society for Neurochemistry
Journal of Neurochemistry
Volume 129, Issue 4, pages 559–572, May 2014
How to Cite
J. Neurochem. (2014) 129, 559–572.
- Issue published online: 23 APR 2014
- Article first published online: 2 JAN 2014
- Accepted manuscript online: 12 DEC 2013 11:19AM EST
- Manuscript Accepted: 9 DEC 2013
- Manuscript Revised: 24 NOV 2013
- Manuscript Received: 2 OCT 2013
- National Institutes of Health. Grant Numbers: AG-23524, AG-18357, AG-31846
- Hanna-Bragard-Apfel Foundation
- Alzheimer Forschung Initiative
- Alzheimer's disease;
- amyloid beta-protein;
- apolipoprotein E;
High serum/plasma cholesterol levels have been suggested as a risk factor for Alzheimer's disease (AD). Some reports, mostly retrospective epidemiological studies, have observed a decreased prevalence of AD in patients taking the cholesterol lowering drugs, statins. The strongest evidence causally linking cholesterol to AD is provided by experimental studies showing that adding/reducing cholesterol alters amyloid precursor protein (APP) and amyloid beta-protein (Aβ) levels. However, there are problems with the cholesterol-AD hypothesis. Cholesterol levels in serum/plasma and brain of AD patients do not support cholesterol as a causative factor in AD. Prospective studies on statins and AD have largely failed to show efficacy. Even the experimental data are open to interpretation given that it is well-established that modification of cholesterol levels has effects on multiple proteins, not only amyloid precursor protein and Aβ. The purpose of this review, therefore, was to examine the above-mentioned issues, discuss the pros and cons of the cholesterol-AD hypothesis, involvement of other lipids in the mevalonate pathway, and consider that AD may impact cholesterol homeostasis.
High serum/plasma cholesterol levels have been suggested as a risk factor for Alzheimer's disease (AD). This Review addresses the Pro's and Con's of whether cholesterol is a causative factor in AD, covering articles ranging from human to cell culture studies, both in vitro and in vivo. Among others, we review models of how abeta could act on a membrane and of how abeta might be perturbing cholesterol in a cell.