载脂蛋白 E 基因型是否应作为阿尔茨海默病临床试验的协变量？
Should the ApoE genotype be a covariate for clinical trials in Alzheimer disease?
机构信息
Department of Neurology, Indiana University School of Medicine, 541 Clinical Drive, CL 291, Indianapolis, IN 46202, USA.
出版信息
Alzheimers Res Ther. 2010 Jun 8;2(3):15. doi: 10.1186/alzrt39.
Abstract
Should the apolipoprotein E (ApoE) genotype be a covariate for clinical trials in Alzheimer disease (AD)? ApoE is a transport protein for lipids, amyloid-beta proteins, and the different phenotypes differentially affect amyloid-beta deposition, neurofibrillary tangle formation, and microglial activation. The ApoE genotype has not affected efficacy in short symptomatic AD trials. ApoE4 has been associated with greater efficacy in at least two mild cognitive impairment studies. Vasogenic edema was more frequent in ApoE4 AD patients treated with a monoclonal antibody to amyloid beta. Since there is evidence that the ApoE genotype may differentially affect disease mechanisms, efficacy, and adverse effects in both AD and mild cognitive impairment trials, the ApoE genotype should be included as a covariate in future studies.
摘要
载脂蛋白 E (ApoE) 基因型是否应作为阿尔茨海默病 (AD) 临床试验的协变量？ApoE 是一种脂质、淀粉样β蛋白的转运蛋白，不同表型会对淀粉样β蛋白沉积、神经纤维缠结形成和小胶质细胞激活产生不同影响。ApoE 基因型并未影响短期有症状 AD 临床试验的疗效。至少有两项轻度认知障碍研究表明，ApoE4 与更高的疗效相关。血管源性水肿在接受淀粉样β单克隆抗体治疗的 ApoE4 AD 患者中更为常见。由于有证据表明 ApoE 基因型可能会对 AD 和轻度认知障碍试验中的疾病机制、疗效和不良反应产生不同影响，因此在未来的研究中，ApoE 基因型应作为协变量纳入其中。
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