Markers of cholesterol metabolism in the brain show stronger associations with cerebrovascular disease than Alzheimer's disease.
Markers of cholesterol metabolism in the brain show stronger associations with cerebrovascular disease than Alzheimer's disease.
复制标题
DOI：
10.3233/jad-2012-111460
复制
发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Rosano C
中科院分区：
文献类型：
--
作者：
Hughes TM;Kuller LH;Lopez OL;Becker JT;Evans RW;Sutton-Tyrrell K;Rosano C
胆固醇代谢被认为在阿尔茨海默病（AD）的发展中起作用。胆固醇的氧化甾醇代谢产物，24S - 羟基胆固醇（24 - OHC，一种脑源性氧化甾醇）和27 - 羟基胆固醇（27 - OHC，一种外周源性氧化甾醇）能穿过血脑屏障，并与阿尔茨海默病相关。我们研究了在认知障碍发生之前，氧化甾醇是否与脑血管疾病的标志物相关。
对来自匹兹堡心血管健康研究认知项目（CHS - CS）的105名参与者（平均年龄为80±4岁）的氧化甾醇进行了定量分析。这些参与者在2002年采血时认知正常，在1992年和1998年进行了磁共振成像（MRI），并且在1998年到2010年期间通过共识会议对阿尔茨海默病发病情况和轻度认知障碍（MCI）进行了年度认知评估。
血浆中24 - OHC水平较高与年龄、性别、先前MRI显示的高级别白质高信号（WMH）以及脑梗死有关。在8年的随访中，血浆24 - OHC水平较高以及24 - OHC/27 - OHC比值较大的参与者也更有可能出现认知障碍。
24 - OHC水平较高表明，在认知障碍发生之前，脑血管疾病患者大脑中的胆固醇代谢增加。
氧化甾醇的测量可能会提供在认知障碍过程中胆固醇代谢和脑部疾病的相关信息。
Cholesterol metabolism is believed to play a role in the development of Alzheimer’s disease (AD). Oxysterol metabolites of cholesterol, 24S-hydroxycholesterol (24-OHC, a brain-derived oxysterol) and 27-hydroxycholesterol (27-OHC, a peripherally derived oxysterol) cross the blood brain barrier and have been associated with Alzheimer’s disease (AD). We investigated whether oxysterols were associated with markers of cerebrovascular disease prior to the onset of cognitive impairment. Oxysterols were quantified in 105 participants (average age was 80±4 years) from the Pittsburgh Cardiovascular Health Study Cognition Study (CHS-CS) who remained cognitively normal at blood draw in 2002, had MRI in 1992 and 1998 and annual cognitive assessment for incident AD and mild cognitive impairment (MCI) made by consensus conference between 1998 and 2010. Higher plasma levels of 24-OHC were associated with age, gender, the presence of high grade white matter hyperintensities (WMH) and brain infarcts on prior MRI. Participants with higher plasma 24-OHC and a greater ratio of 24-OHC/27-OHC were also more likely to develop incident cognitive impairment over 8 years of follow-up. Higher levels of 24-OHC suggest increased cholesterol metabolism occurring in the brains of participants with cerebrovascular disease prior to the onset of cognitive impairment. Measurement of oxysterols may provide information about cholesterol metabolism and brain disease over the cognitive impairment process.