University of California, Davis.
University of California, Berkeley.
JAMA Neurol. 2014 Feb;71(2):195-200. doi: 10.1001/jamaneurol.2013.5390.
Because deposition of cerebral β-amyloid (Aβ) seems to be a key initiating event in Alzheimer disease (AD), factors associated with increased deposition are of great interest. Whether elevated serum cholesterol levels act as such a factor is unknown.
To investigate the association between serum cholesterol levels and cerebral Aβ during life early in the AD process.
DESIGN, SETTING, AND PARTICIPANTS: A multisite, university medical center-based, cross-sectional analysis of potential associations between contemporaneously assayed total serum cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and cerebral Aβ, measured with carbon C11-labeled Pittsburgh Compound B (PIB) positron emission tomography. Seventy-four persons (mean age, 78 years) were recruited via direct outreach in stroke clinics and community senior facilities following a protocol designed to obtain a cohort enriched for cerebrovascular disease and elevated vascular risk. Three patients had mild dementia. All others were clinically normal (n = 33) or had mild cognitive impairment (n = 38).
Cerebral Aβ was quantified using a Global PIB Index, which averages PIB retention in cortical areas prone to amyloidosis. Statistical models that controlled for age and the apolipoprotein E ε4 allele revealed independent associations among the levels of LDL-C, HDL-C, and PIB index. Higher LDL-C and lower HDL-C levels were both associated with a higher PIB index. No association was found between the total cholesterol level and PIB index. No association was found between statin use and PIB index, and controlling for cholesterol treatment in the statistical models did not alter the basic findings.
Elevated cerebral Aβ level was associated with cholesterol fractions in a pattern analogous to that found in coronary artery disease. This finding, in living humans, is consistent with prior autopsy reports, epidemiologic findings, and animal and in vitro work, suggesting an important role for cholesterol in Aβ processing. Because cholesterol levels are modifiable, understanding their link to Aβ deposition could potentially and eventually have an effect on retarding the pathologic cascade of AD. These findings suggest that understanding the mechanisms through which serum lipids modulate Aβ could offer new approaches to slowing Aβ deposition and thus to reducing the incidence of AD.
由于脑β-淀粉样蛋白（Aβ）的沉积似乎是阿尔茨海默病（AD）的一个关键起始事件，因此与沉积增加相关的因素非常重要。目前尚不清楚升高的血清胆固醇水平是否就是这样的一个因素。
研究 AD 早期生活中血清胆固醇水平与脑 Aβ之间的关系。
设计、地点和参与者：这是一项多地点、以大学医疗中心为基础的研究，对同时测定的总血清胆固醇、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）与用碳 C11 标记的匹兹堡化合物 B（PIB）正电子发射断层扫描（PET）测量的脑 Aβ之间的潜在关联进行了横断面分析。74 名参与者（平均年龄 78 岁）通过直接联系中风诊所和社区老年人设施招募，采用了一项旨在获得脑血管疾病和血管风险升高的队列的方案。3 名患者有轻度痴呆。其余所有人均为临床正常（n=33）或轻度认知障碍（n=38）。
使用平均皮质区 PIB 保留量的全脑 PIB 指数来量化脑 Aβ。控制年龄和载脂蛋白 E ε4 等位基因的统计学模型揭示了 LDL-C、HDL-C 和 PIB 指数之间的独立关联。较高的 LDL-C 和较低的 HDL-C 水平与较高的 PIB 指数相关。总胆固醇水平与 PIB 指数之间没有关联。他汀类药物的使用与 PIB 指数之间没有关联，并且在统计学模型中控制胆固醇治疗并没有改变基本发现。
在生活在人类中的，脑 Aβ 水平与胆固醇分数之间的关联与在冠状动脉疾病中发现的模式相似。这一发现与先前的尸检报告、流行病学发现以及动物和体外研究一致，表明胆固醇在 Aβ 处理中起着重要作用。由于胆固醇水平是可改变的，因此了解其与 Aβ 沉积的关系可能最终会对延缓 AD 的病理级联反应产生影响。这些发现表明，了解血清脂质调节 Aβ 的机制可以提供减缓 Aβ 沉积的新方法，从而降低 AD 的发病率。
