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Link between heart disease, cholesterol, and Alzheimer's disease: A review

2000; Wiley; Volume: 50; Issue: 4 Linguagem: Inglês

10.1002/1097-0029(20000815)50

1097-0029

D. Larry Sparks, Timothy A. Martin, David Groß, John C. Hunsaker,

Nuclear Receptors and Signaling

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.