Plasma Aβ as a biomarker for predicting Aβ-PET status in Alzheimer's disease:a systematic review with meta-analysis

Objective Amyloid-beta positron emission tomography (A beta-PET) scan has been proposed to detect amyloid-beta (A beta) deposition in the brain. However, this approach is costly and not ideal for the early diagnosis of Alzheimer's disease. Blood-based A beta measurement offers a scalable alternative to the costly or invasive biomarkers. The aim of this study was to statistically validate whether plasma A beta could predict A beta-PET status via meta-analysis. Methods We systematically searched for eligible studies from PubMed, Embase and Cochrane Library, which reported plasma A beta levels of amyloid-beta positron emission tomography-positive (PET (+)) and amyloid-beta positron emission tomography-negative (PET (-)) subjects. We generated pooled estimates using random effects meta-analyses. For any study that has significant heterogeneity, metaregression and subgroup analysis were further conducted. Publication bias was appraised by funnel plots and Egger's test. Results 16 studies with 3047 participants were included in the meta-analysis. Among all the enrolled studies, 10 studies reported plasma A beta 40 values, while 9 studies reported plasma A beta 42 values and 13 studies reported A beta 42/A beta 40 ratio. The pooled standardised mean difference (SMD) was 0.76 (95% CI -0.61 to 2.14, p=0.28) in the plasma A beta 40 values group. Plasma A beta 42 values group has a pooled SMD of -0.60 (95% CI -0.80 to -0.41, p<0.0001). In the plasma A beta 42/A beta 40 ratio group, the pooled SMD was -1.44 (95% CI -2.17 to -0.72, p<0.0001). Conclusion Plasma A beta 40 values might not distinguish between PET (+) and PET (-) people. However, plasma A beta 42 values and plasma A beta 42/A beta 40 ratio could be served as independent biomarkers for predicting A beta-PET status.