Haight Thaddeus, Bryan R Nick, Meirelles Osorio, Tracy Russell, Fornage Myriam, Richard Melissa, Nasrallah Ilya, Yaffe Kristine, Jacobs David R, Lewis Cora, Schreiner Pamela, Sidney Stephen, Davatzikos Christos, Launer Lenore J
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MD United States of America.
Department of Radiology, University of Pennsylvania Health System, Philadelphia, PA United States of America.
PLoS One. 2018 Jan 11;13(1):e0190478. doi: 10.1371/journal.pone.0190478. eCollection 2018.
Clinical and epidemiological studies of older persons have implicated clusterin in Alzheimer's disease (AD) pathogenesis. In the context of identifying early biomarkers of risk, we examined associations of plasma clusterin and characteristics of AD in middle-aged individuals from the community.
Subjects were 639 cognitively normal individuals (mean age 50 ± 3.5) from the Coronary Artery Risk Development in Young Adults (CARDIA) Brain MRI sub-study. Clusterin was quantified using ELISA (mean 255± 31 ng/ml). Associations were assessed between clusterin and volumes of brain regions known to atrophy in early AD, including entorhinal cortex (ECV), hippocampus (HV), and medial temporal lobe (MTLV) volumes (cm3). Total brain volume (TBV) and volumes of structures affected in later AD were examined for comparison.
In multivariable models, higher clusterin had a negative non-linear association with ECV (combined left and right hemispheres), and this association was influenced by the highest clusterin levels. Compared to mean clusterin, 1 and 2 standard deviation (SD) level increases in clusterin were associated with -2.1% (95% CI: -3.3,-0.9) and -7.3% (95% CI: -11.3,-3.3) lower ECV, respectively. Similar relationships were observed between clusterin and HV, although the relationship was stronger for left-side HV than the right-side. However, the association was not significant after adjusting for covariates. Negative non-linear associations between clusterin and MTLV were strongest for the left side: compared to mean clusterin, 1 and 2 SD level increases in clusterin were associated with -0.9% (95% CI: -1.9, 0.1) and -3.7% (95% CI: -7.1, -0.3) lower MTLV. There were no significant associations between clusterin and brain structures affected in later AD.
In middle-aged adults unselected for AD, plasma clusterin was associated with lower volume of the entorhinal cortex, an area that atrophies early in AD. Clusterin could be informative as part of a multi-component preclinical marker for AD.
针对老年人的临床和流行病学研究表明，簇集蛋白与阿尔茨海默病（AD）的发病机制有关。在识别早期风险生物标志物的背景下，我们研究了社区中年个体血浆簇集蛋白与AD特征之间的关联。
研究对象为来自青年动脉粥样硬化风险发展研究（CARDIA）脑MRI子研究的639名认知正常个体（平均年龄50±3.5岁）。使用酶联免疫吸附测定法（ELISA）对簇集蛋白进行定量（平均255±31 ng/ml）。评估簇集蛋白与已知在早期AD中会萎缩的脑区体积之间的关联，包括内嗅皮质（ECV）、海马体（HV）和内侧颞叶（MTLV）体积（cm³）。还检查了全脑体积（TBV）以及后期AD中受影响结构的体积以作比较。
在多变量模型中，较高的簇集蛋白水平与ECV（左右半球合并）呈负非线性关联，且这种关联受最高簇集蛋白水平影响。与平均簇集蛋白水平相比，簇集蛋白水平升高1个和2个标准差（SD）分别与ECV降低2.1%（95%CI：-3.3，-0.9）和7.3%（95%CI：-11.3，-3.3）相关。在簇集蛋白与HV之间也观察到类似关系，尽管左侧HV的关系比右侧更强。然而，在调整协变量后，这种关联并不显著。簇集蛋白与MTLV之间的负非线性关联在左侧最为明显：与平均簇集蛋白水平相比，簇集蛋白水平升高1个和2个SD分别与MTLV降低0.9%（95%CI：-1.9，0.1）和3.7%（95%CI：-7.1，-0.3）相关。簇集蛋白与后期AD中受影响的脑结构之间无显著关联。
在未筛选出AD的中年成年人中，血浆簇集蛋白与内嗅皮质体积减小有关，内嗅皮质是AD早期会萎缩的区域。簇集蛋白作为AD多组分临床前标志物的一部分可能具有参考价值。
