阿尔茨海默病临床试验中的纵向血浆淀粉样蛋白β
Longitudinal plasma amyloid beta in Alzheimer's disease clinical trials.
作者信息
Donohue Michael C, Moghadam Setareh H, Roe Allyson D, Sun Chung-Kai, Edland Steven D, Thomas Ronald G, Petersen Ronald C, Sano Mary, Galasko Douglas, Aisen Paul S, Rissman Robert A
机构信息
Alzheimer's Disease Cooperative Study, Department of Neurosciences, University of California San Diego, School of Medicine, San Diego, CA, USA; Department of Family Preventive Medicine, University of California San Diego, School of Medicine, San Diego, CA, USA.
Alzheimer's Disease Cooperative Study, Department of Neurosciences, University of California San Diego, School of Medicine, San Diego, CA, USA.
出版信息
Alzheimers Dement. 2015 Sep;11(9):1069-79. doi: 10.1016/j.jalz.2014.07.156. Epub 2014 Oct 7.
INTRODUCTION
Little is known about the utility of plasma amyloid beta (Aβ) in clinical trials of Alzheimer's disease (AD).
METHODS
We analyzed longitudinal plasma samples from two large multicenter clinical trials: (1) donezepil and vitamin E in mild cognitive impairment (n = 405, 24 months) and (2) simvastatin in mild to moderate AD (n = 225, 18 months).
RESULTS
Baseline plasma Aβ was not related to cognitive or clinical progression. We observed a decrease in plasma Aβ40 and 42 among apolipoprotein E epsilon 4 (APOE ε4) carriers relative to noncarriers in the mild cognitive impairment trial. Patients treated with simvastatin showed a significant increase in Aβ compared with placebo. We found significant storage time effects and considerable plate-to-plate variation.
DISCUSSION
We found no support for the utility of plasma Aβ as a prognostic factor or correlate of cognitive change. Analysis of stored specimens requires careful standardization and experimental design, but plasma Aβ may prove useful in pharmacodynamic studies of antiamyloid drugs.
引言
关于血浆淀粉样蛋白β（Aβ）在阿尔茨海默病（AD）临床试验中的效用，人们了解甚少。
方法
我们分析了来自两项大型多中心临床试验的纵向血浆样本：（1）多奈哌齐和维生素E治疗轻度认知障碍（n = 405，24个月）；（2）辛伐他汀治疗轻度至中度AD（n = 225，18个月）。
结果
基线血浆Aβ与认知或临床进展无关。在轻度认知障碍试验中，相对于非载脂蛋白Eε4（APOE ε4）携带者，我们观察到APOE ε4携带者的血浆Aβ40和42有所下降。与安慰剂相比，接受辛伐他汀治疗的患者Aβ显著增加。我们发现了显著的储存时间效应和相当大的板间差异。
讨论
我们没有发现血浆Aβ作为预后因素或认知变化相关因素的效用的证据。对储存标本的分析需要仔细的标准化和实验设计，但血浆Aβ可能在抗淀粉样蛋白药物的药效学研究中证明有用。
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