Link between heart disease, cholesterol, and Alzheimer's disease: a review.
Increased prevalence of Alzheimer's disease-like beta-amyloid deposits in the neuropil and within neurons occurs in the brains of non-demented individuals with heart disease. Heart disease is a prevalent finding in Alzheimer's disease, and may be a forerunner to the dementing disorder. In the cholesterol-fed rabbit model of human coronary heart disease there is production and accumulation of beta-amyloid in the brain. This accumulation of beta-amyloid can be reversed by removing cholesterol from the rabbits' diet. In culture cells, a cholesterol challenge has been shown to increase production of beta-amyloid, and dramatic reductions of cholesterol produced by HMG Co-A reductase inhibitors decrease production of beta-amyloid. Increased beta-amyloid production is also produced by dietary cholesterol in a number of transgenic mouse models of Alzheimer's disease. Administration of HMG Co-A reductase inhibitors may block beta-amyloid production caused by dietary cholesterol in rabbits. Clinical trials testing the benefit of HMG Co-A reductase inhibitors in the treatment of Alzheimer's disease are underway.
Haldeman Laboratory for Alzheimer's Disease Research, Sun Health Research Institute, Sun City, Arizona, USA. Lsparks@mail.sunhealth.org
D L
DL
Sparks
T A
TA
Martin
D R
DR
Gross
J C
JC
Hunsaker
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D004195:Disease Models, Animal; D006331:Heart Diseases / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology
D016229:Amyloid beta-Peptides; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002784:Cholesterol