A systematic review and meta-analysis of plasma amyloid 1-42 and tau as biomarkers for Alzheimer’s disease

OBJECTIVE Amyloid 1-42 (Aβ42) and tau in cerebrospinal fluid are currently used as markers for diagnosis of Alzheimer's disease. Conflicting reports exist regarding their plasma levels in Alzheimer's disease patients. A meta-analysis was performed to statistically validate the use of plasma Aβ42 and tau as biomarkers for Alzheimer's disease. METHODS Different databases were searched using the search key: (amyloid OR amyloid1-42 OR Aβ42) AND (tau OR total tau) AND plasma AND (alzheimer's OR alzheimer's disease), and for databases not accepting boolean search, records were retrieved using the search key: plasma + amyloid + tau + alzheimer's. A total of 1880 articles for Aβ42 and 1508 articles for tau were shortlisted. The abstracts were screened, and 69 articles reporting plasma Aβ42 levels and 6 articles reporting plasma tau were identified. After exclusion, 25 studies reporting plasma Aβ42 and 6 studies reporting total tau were analysed in Review Manager version 5.2 using weighted mean difference method, and the bias between studies was assessed using the funnel plot. RESULTS Plasma Aβ42 and tau did not vary significantly between Alzheimer's disease patients and controls. The funnel plot showed that there was no bias between studies for Aβ42, while possible bias existed for tau due to availability of limited studies. CONCLUSION This analysis pinpoints that plasma Aβ42 and tau could not serve as reliable markers independently for diagnosis of Alzheimer's disease and a cohort study with age, sex and apolipoprotein E correction is warranted for their possible use as Alzheimer's disease markers.