Relationship of amyloid-β1-42 in blood and brain amyloid: Ginkgo Evaluation of Memory Study
Relationship of amyloid-β1-42 in blood and brain amyloid: Ginkgo Evaluation of Memory Study
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DOI：
10.1093/braincomms/fcz038
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发表时间：
2020-01-01
影响因子：
4.8
通讯作者：
Kuller, Lewis H.
中科院分区：
文献类型：
--
作者：
Lopez, Oscar L.;Klunk, William E.;Kuller, Lewis H.
预测大脑中淀粉样斑块范围和阿尔茨海默病风险的血液测试对于早期识别痴呆和阿尔茨海默病的较高风险以及评估新的预防疗法具有重要意义。本研究的目的是确定匹兹堡银杏记忆评估研究中心参与者的血浆β-淀粉样蛋白1-42、1-40水平和β-淀粉样蛋白1-42/1-40比率是否与2009年使用匹兹堡化合物-B PET成像测量的脑纤维状淀粉样蛋白斑块的范围、海马体积、颞叶和白斑的皮质厚度相关。物质病变。 2009 年，共有 194 名参与者进行了匹兹堡化合物 B 测量，平均年龄为 85 岁； 96% 是白人，60% 是男性。匹兹堡化合物-B 阳性定义为标准化摄取值比率 >= 1.57。使用礼来公司开发并在佛蒙特大学修改的夹心酶联免疫吸附测定法测量血液中的淀粉样蛋白。截至 2008 年研究结束时，所有参与者都没有痴呆。研究样本包括 2000 年 2 月抽取的 160 份血液样本和 2009 年抽取的 133 份血液样本，并在 2009 年测量了脑淀粉样蛋白。所有血液样本均在 2009 年同一时间进行分析。血浆淀粉样蛋白-β 1-42 与匹兹堡化合物-B 阳性百分比呈负相关（标准化摄取值比 >= 1.57），β = 0.04， P = 0.005。实际上，所有年龄较大时载脂蛋白 E4 呈阳性的参与者，纤维状淀粉样蛋白的匹兹堡化合物 B 也呈阳性。在载脂蛋白-E4 阴性参与者中，淀粉样蛋白-β 1-42 的四分位数与匹兹堡化合物-B 阳性呈负相关。在多元回归模型中，2000-02 或 2009 年测量的血浆淀粉样蛋白-β 1-42 与匹兹堡化合物-B 阳性呈显着负相关，淀粉样蛋白-β 1-42/1-40 比率也是如此。与多重 Logistic 模型中的第四个四分位数相比，2009 年大脑中淀粉样蛋白-β 1-42 第一个四分位数出现匹兹堡化合物 B 阳性的比值比增加了 4 倍。这是首批纵向研究之一，旨在评估血液中的淀粉样蛋白 β 1-42 与使用匹兹堡化合物 B 进行 PET 成像测量的大脑淀粉样蛋白沉积程度之间的关系。我们的研究结果表明，在认知正常个体中，远期和近期较低的血浆淀粉样蛋白-β 1-42 水平与大脑淀粉样蛋白沉积呈负相关。然而，随着时间的推移（8 年），血浆淀粉样蛋白-β 1-42 的变化很小，并且与匹兹堡化合物-B 的量无关。
A blood test that predicts the extent of amyloid plaques in the brain and risk of Alzheimer's disease would have important benefits for the early identification of higher risk of dementia and Alzheimer's disease and the evaluation of new preventative therapies. The goal of this study was to determine whether plasma levels of amyloid-beta 1-42, 1-40 and the amyloid-beta 1-42/1-40 ratio among participants in the Pittsburgh centre of the Ginkgo Evaluation of Memory Study were related to the extent of brain fibrillar amyloid plaques measured in 2009 using Pittsburgh compound-B PET imaging, hippocampal volume, cortical thickness in the temporal lobe and white matter lesions. There were 194 participants who had Pittsburgh compound-B measurements in 2009 with the mean age of 85 years; 96% were white and 60% men. Pittsburgh compound-B positivity was defined as a standardized uptake value ratio of >= 1.57. Amyloid-beta in blood was measured using a sandwich enzyme-linked immunosorbent assay developed by Eli Lilly and modified at the University of Vermont. All participants were nondemented as of 2008 at the time of study close out. The study sample included 160 with blood samples drawn in 2000-02 and 133 from 2009 and also had brain amyloid measured in 2009. All blood samples were analysed at the same time in 2009. Plasma amyloid-beta 1-42 was inversely related to the percent Pittsburgh compound-B positive (standardized uptake value ratio >= 1.57), beta = 0.04, P = 0.005. Practically all participants who were apolipoprotein-E4 positive at older ages were also Pittsburgh compound-B positive for fibrillar amyloid. Among apolipoprotein-E4-negative participants, quartiles of amyloid-beta 1-42 were inversely related to Pittsburgh compound-B positivity. In multiple regression models, plasma amyloid-beta 1-42 measured in 2000-02 or 2009 were significantly and inversely related to Pittsburgh compound-B positivity as was the amyloid-beta 1-42/1-40 ratio. There was a 4-fold increase in the odds ratio for the presence of Pittsburgh compound-B positivity in the brain in 2009 for the first quartile of amyloid-beta 1-42 as compared with the fourth quartile in the multiple logistic model. This is one of the first longitudinal studies to evaluate the relationship between amyloid-beta 1-42 in the blood and the extent of brain amyloid deposition measured by PET imaging using Pittsburgh compound-B. Our findings showed that remote and recent low plasma amyloid-beta 1-42 levels were inversely associated with brain amyloid deposition in cognitively normal individuals. However, changes in plasma amyloid-beta 1-42 over time (8 years) were small and not related to the amount of Pittsburgh compound-B.