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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.