Medical Histories of Control Subjects Influence the Biomarker Potential of Plasma Aβ in Alzheimer's Disease: a Meta-analysis

Whether blood amyloid-beta (A beta) could be a peripheral biomarker of Alzheimer's disease (AD) remains in dispute. In the present study, we conducted a meta-analysis with 19 citations searched from Embase, PubMed, and the Cochrane Library database. Weighted mean difference (WMD) with 95% confidence intervals (CIs) was used to estimate the effect size. We firstly analyzed the plasma A beta(40), A beta(42), and A beta(42)/A beta(40) ratio in AD and control group subjects. However, only a lower level of plasma A beta(42) was figured out in AD group subjects with weak statistical significance (WMD 1.82; 95% CI 0.59, 3.06; P = 0.004; I-2 = 84%). We considered that the medical histories of control subjects could influence the biomarker ability of plasma A beta. Therefore, subgroup analyses were then carried out based on a new recruiting criterion for control subjects, defining as no afflictions of any A beta-related diseases. Surprisingly, AD group subjects showed a significant decrease in plasma A beta(42)/A beta(40) ratio with low heterogeneity among studies (WMD 0.02; 95% CI 0.02, 0.02; P < 0.00001; I-2 = 0%). Moreover, not only the A beta(42)/A beta(40) ratio but also A beta(42) and A beta(40) were indifferent between AD and pseudo-control subjects which might be afflicted with A beta-related diseases. This meta-analysis demonstrated that medical histories of control subjects were interference factors impeding plasma A beta to be a biomarker of AD.