Predictive Accuracy of Blood-Derived Biomarkers for Amyloid-β Brain Deposition Along with the Alzheimer's Disease Continuum: A Systematic Review

Background: An amyloid-beta (A beta) positron emission tomography (A beta-PET) scan of the human brain could lead to an early diagnosis of Alzheimer's disease (AD) and estimate disease progression. However, A beta-PET imaging is expensive, invasive, and rarely applicable to cognitively normal subjects at risk for dementia. The identification of blood biomarkers predictive of A beta brain deposition could help the identification of subjects at risk for dementia and could be helpful for the prognosis of AD progression. Objective: This study aimed to analyze the prognostic accuracy of blood biomarkers in predicting A beta-PET status along with progression toward AD. Methods: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched bibliographic databases from 2010 to 2020. The quality of the included studies was assessed by the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Results: A total of 8 studies were retrieved. The prognostic accuracy of A beta-PET status was calculated by obtaining ROCs for the following biomarkers: free, total, and bound A beta(42) and A beta(40); A beta(42/40) ratio; neurofilaments (NFL); total tau (T-tau); and phosphorylated-tau181 (P-tau181). Higher and lower plasma baseline levels of P-tau181 and the A beta(42/40) ratio, respectively, showed consistently good prognostication of A beta-PET brain accumulation. Only P-tau181 was shown to predict AD progression. Conclusion: In conclusion, the A beta(42/40) ratio and plasma P-tau181 were shown to predict A beta-PET status. Plasma P-tau181 could also be a preclinical biomarker for AD progression.