Koyama Alain, Okereke Olivia I, Yang Ting, Blacker Deborah, Selkoe Dennis J, Grodstein Francine
Department of Psychiatry, University of California at San Francisco, USA.
Arch Neurol. 2012 Jul;69(7):824-31. doi: 10.1001/archneurol.2011.1841.
Preclinical prediction of Alzheimer disease (AD) is important and critical to effective intervention. Plasma levels of amyloid-β (Aβ) peptides have been a principal focus of the growing literature on blood-based biomarkers, but studies to date have varied in design, assay methods, and sample size, making it difficult to readily interpret the overall data.
To conduct a systematic review and meta-analysis of relevant prospective studies to determine whether plasma amyloid-β levels may predict development of dementia, AD, and cognitive decline.
We searched prospective studies published between 1995 and 2011 indexed in the MEDLINE, EMBASE, and PsycINFO databases. Selected studies included those measuring at least 1 relevant plasma amyloid-β species (Aβ(40), Aβ(42), or Aβ(42):Aβ(40) ratio) and reporting an effect estimate for dementia, AD, or cognitive change.
Using a standardized extraction form, appropriate study parameters on subject information, exposure, and outcome were extracted. Random effects models were used to generate summary risk ratios and 95% confidence intervals comparing the bottom vs top quantiles for each plasma measure.
Thirteen studies with a total of 10 303 subjects met inclusion criteria for meta-analysis. Lower Aβ(42):Aβ(40) ratios were significantly associated with development of AD (summary risk ratio, 1.60; 95% CI, 1.04-2.46; P = .03) and dementia (risk ratio, 1.67; 95% CI, 1.02-2.75; P = .04). Significant heterogeneity was found for both summary estimates, which could not be explained by participants' age, sex distribution, the study's follow-up time, or year of publication. Plasma levels of Aβ(40) and Aβ(42) alone were not significantly associated with either outcome.
Overall, the literature indicates that plasma Aβ(42):Aβ(40) ratios predict development of AD and dementia. However, significant heterogeneity in the meta-analysis underlines the need for substantial further investigation of plasma amyloid-β levels as a preclinical biomarker.
阿尔茨海默病（AD）的临床前预测对于有效干预至关重要。淀粉样β蛋白（Aβ）肽的血浆水平一直是关于血液生物标志物的大量文献的主要关注点，但迄今为止的研究在设计、检测方法和样本量方面存在差异，使得难以轻易解读总体数据。
对相关前瞻性研究进行系统评价和荟萃分析，以确定血浆淀粉样β水平是否可预测痴呆、AD和认知功能下降的发生。
我们检索了1995年至2011年期间在MEDLINE、EMBASE和PsycINFO数据库中索引的前瞻性研究。入选研究包括那些测量至少1种相关血浆淀粉样β物质（Aβ(40)、Aβ(42)或Aβ(42):Aβ(40)比值）并报告痴呆、AD或认知变化效应估计值的研究。
使用标准化提取表，提取关于受试者信息、暴露和结局的适当研究参数。采用随机效应模型生成汇总风险比和95%置信区间，比较每种血浆测量值的最低与最高四分位数。
13项研究共10303名受试者符合荟萃分析的纳入标准。较低的Aβ(42):Aβ(40)比值与AD的发生（汇总风险比，1.60；95%置信区间，1.04 - 2.46；P = 0.03）和痴呆（风险比，1.67；95%置信区间，1.02 - 2.75；P = 0.04）显著相关。两种汇总估计值均存在显著异质性，这不能通过参与者的年龄、性别分布、研究的随访时间或发表年份来解释。单独的Aβ(40)和Aβ(42)血浆水平与任何一种结局均无显著相关性。
总体而言，文献表明血浆Aβ(42):Aβ(40)比值可预测AD和痴呆的发生。然而，荟萃分析中的显著异质性强调了作为临床前生物标志物的血浆淀粉样β水平需要大量进一步研究。
