Department of Clinical and Biological Sciences, Faculty of Medicine San Luigi Gonzaga, University of Turin, Turin, Italy.
Ann N Y Acad Sci. 2012 Jul;1259:54-64. doi: 10.1111/j.1749-6632.2012.06513.x.
Alzheimer's disease (AD), the most common form of dementia, is characterized by the progressive loss of neurons and synapses, and by extracellular deposits of amyloid-β (Aβ) as senile plaques, Aβ deposits in the cerebral blood vessels, and intracellular inclusions of hyperphosphorylated tau in the form of neurofibrillary tangles. Several mechanisms contribute to AD development and progression, and increasing epidemiological and molecular evidence suggests a key role of cholesterol in its initiation and progression. Altered cholesterol metabolism and hypercholesterolemia appear to play fundamental roles in amyloid plaque formation and tau hyperphosphorylation. Over the last decade, growing evidence supports the idea that cholesterol oxidation products, known as oxysterols, may be the missing link between altered brain cholesterol metabolism and AD pathogenesis, as their involvement in neurotoxicity, mainly by interacting with Aβ peptides, is reported.
阿尔茨海默病（AD）是最常见的痴呆症形式，其特征是神经元和突触逐渐丧失，以及细胞外淀粉样β（Aβ）沉积形成老年斑、Aβ在脑血管中的沉积以及过度磷酸化的tau 以神经原纤维缠结的形式在细胞内的包含物。几种机制有助于 AD 的发展和进展，越来越多的流行病学和分子证据表明胆固醇在其起始和进展中起关键作用。胆固醇代谢改变和高胆固醇血症似乎在淀粉样斑块形成和 tau 过度磷酸化中起重要作用。在过去的十年中，越来越多的证据支持这样一种观点，即胆固醇氧化产物，称为氧化固醇，可能是改变的大脑胆固醇代谢与 AD 发病机制之间缺失的联系，因为据报道它们的参与神经毒性，主要是通过与 Aβ肽相互作用。
