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

Amyloid-β positron emission tomography (Aβ-PET) scan has been proposed to detect amyloid-β (Aβ) deposition in the brain. However, this approach is costly and not ideal for the early diagnosis of Alzheimer's disease. Blood-based Aβ measurement offers a scalable alternative to the costly or invasive biomarkers. The aim of this study was to statistically validate whether plasma Aβ could predict Aβ-PET status via meta-analysis.

We systematically searched for eligible studies from PubMed, Embase and Cochrane Library, which reported plasma Aβ levels of amyloid-β positron emission tomography-positive (PET (+)) and amyloid-β 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.

16 studies with 3047 participants were included in the meta-analysis. Among all the enrolled studies, 10 studies reported plasma Aβ40 values, while 9 studies reported plasma Aβ42 values and 13 studies reported Aβ42/Aβ40 ratio. The pooled standardised mean difference (SMD) was 0.76 (95% CI -0.61 to 2.14, p=0.28) in the plasma Aβ40 values group. Plasma Aβ42 values group has a pooled SMD of -0.60 (95% CI -0.80 to -0.41, p<0.0001). In the plasma Aβ42/Aβ40 ratio group, the pooled SMD was -1.44 (95% CI -2.17 to -0.72, p<0.0001).

Plasma Aβ40 values might not distinguish between PET (+) and PET (-) people. However, plasma Aβ42 values and plasma Aβ42/Aβ40 ratio could be served as independent biomarkers for predicting Aβ-PET status.