Sparks D L, Martin T A, Gross D R, Hunsaker J C
Haldeman Laboratory for Alzheimer's Disease Research, Sun Health Research Institute, Sun City, Arizona, USA.
Microsc Res Tech. 2000 Aug 15;50(4):287-90. doi: 10.1002/1097-0029(20000815)50:4<287::AID-JEMT7>3.0.CO;2-L.
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.
在患有心脏病的非痴呆个体大脑中，神经毡和神经元内类似阿尔茨海默病的β-淀粉样蛋白沉积物的患病率增加。心脏病在阿尔茨海默病中很常见，可能是这种痴呆症的先兆。在人类冠心病的胆固醇喂养兔模型中，大脑中会产生并积累β-淀粉样蛋白。从兔子饮食中去除胆固醇可逆转这种β-淀粉样蛋白的积累。在培养细胞中，胆固醇刺激已被证明会增加β-淀粉样蛋白的产生，而HMG Co-A还原酶抑制剂显著降低胆固醇的产生会减少β-淀粉样蛋白的产生。在一些阿尔茨海默病转基因小鼠模型中，饮食中的胆固醇也会增加β-淀粉样蛋白的产生。给予HMG Co-A还原酶抑制剂可能会阻断兔子饮食中胆固醇引起的β-淀粉样蛋白产生。正在进行测试HMG Co-A还原酶抑制剂治疗阿尔茨海默病疗效的临床试验。
