Brain cholesterol metabolism, oxysterols, and dementia.
Brain cholesterol metabolism, oxysterols, and dementia.
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脑胆固醇代谢，氧甲醇和痴呆。
DOI：
10.3233/jad-2012-121585
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Kuller LH
中科院分区：
文献类型：
--
作者：
Hughes TM;Rosano C;Evans RW;Kuller LH
胆固醇代谢与阿尔茨海默病（AD）的病因学和脑中淀粉样蛋白的产生有关。虽然脑胆固醇不能在体内直接测量，但氧化固醇，24 S-羟基胆固醇（24-OHC）是脑胆固醇的主要代谢物，可以在血液中测量。本综述的目的是评估血浆24-OHC作为AD风险的潜在生物标志物，并讨论其在大脑和血液中水平的相关因素。本系统性综述使用以下关键词（“24 S-羟基胆固醇”或“24-羟基胆固醇”）和（“大脑”或“认知”）检查了1950年至2012年6月期间发表的研究，这些研究检查了血浆24-OHC、认知、大脑结构和痴呆之间的关系。我们共发现了28项关于血浆24-OHC和神经退行性疾病的研究，其中包括12项将痴呆症作为临床终点的研究。这些研究在观察到的关联方向上各不相同。结果表明，与认知正常对照组相比，认知障碍早期的血浆24-OHC可能较高，而AD晚期的血浆24-OHC可能较低。血液中24-OHC的测量可能是大脑胆固醇代谢和AD风险的重要潜在标志物。对血浆24-OHC和痴呆的进一步研究必须考虑疾病的阶段，建立氧固醇浓度的时间趋势，并采用神经影像学方式来评估认知障碍发作前大脑中发生的结构和代谢变化。
Cholesterol metabolism is implicated in the etiology of Alzheimer’s disease (AD) and amyloid production in the brain. While brain cholesterol cannot be measured directly in vivo, the oxysterol, 24S-hydroxycholesterol (24-OHC), is the predominant metabolite of brain cholesterol and can be measured in the blood. The aim of this review is to evaluate plasma 24-OHC as a potential biomarker of AD risk and discuss factors related to its levels in the brain and blood. This systematic review examines studies published between 1950 and June 2012 that examined the relationship between plasma 24-OHC, cognition, brain structure, and dementia using the following key words (“24S-hydroxycholesterol” or “24-hydroxycholesterol”) and (“Brain” or “Cognitive”). We found a total of 28 studies of plasma 24-OHC and neurodegenerative disease, including a subset of 12 that used dementia as a clinical endpoint. These studies vary in the direction of the observed associations. Results suggest plasma 24-OHC may be higher in the early stages of cognitive impairment and lower in more advanced stages of AD when compared to cognitively normal controls. Measures of 24-OHC in the blood may be an important potential marker for cholesterol metabolism in the brain and risk of AD. Further studies of plasma 24-OHC and dementia must account for the stage of disease, establish the temporal trends in oxysterol concentrations, and employ neuroimaging modalities to assess the structural and metabolic changes occurring in the brain prior to the onset of cognitive impairment.