Geriatric Research, Education and Clinical Center, VAMC, Department of Pharmacology, University of Minnesota School of Medicine, Minneapolis, Minnesota, USA.
J Neurochem. 2014 May;129(4):559-72. doi: 10.1111/jnc.12637. Epub 2014 Jan 2.
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 (Ab) 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 Ab. 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.
血清/血浆胆固醇水平升高被认为是阿尔茨海默病（AD）的一个危险因素。一些报告，主要是回顾性的流行病学研究，观察到服用降胆固醇药物他汀类药物的患者 AD 的患病率降低。胆固醇与 AD 之间存在因果关系的最强证据来自于实验研究，这些研究表明，增加/减少胆固醇会改变淀粉样前体蛋白（APP）和淀粉样β蛋白（Ab）的水平。然而，胆固醇与 AD 的假说存在一些问题。AD 患者的血清/血浆和大脑中的胆固醇水平并不支持胆固醇是 AD 的致病因素。关于他汀类药物和 AD 的前瞻性研究在很大程度上未能显示出其疗效。即使是实验数据也存在争议，因为众所周知，胆固醇水平的改变会对多种蛋白质产生影响，而不仅仅是淀粉样前体蛋白和 Ab。因此，本综述的目的是检查上述问题，讨论胆固醇与 AD 假说的利弊，以及甲羟戊酸途径中其他脂质的参与，并考虑 AD 可能影响胆固醇的动态平衡。
