Blood-Based β-Amyloid and Phosphorylated Tau (p-Tau) Biomarkers in Alzheimer’s Disease: A Systematic Review of Their Diagnostic Potential

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and neuropathological features such as amyloid-β (Aβ) plaques and phosphorylated tau (p-Tau) tangles. Blood-based biomarkers of Aβ and p-Tau have emerged as promising tools for early diagnosis, monitoring, and risk stratification of AD. This systematic review evaluates current evidence on the diagnostic utility of Aβ and p-Tau blood biomarkers in AD. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive literature search was conducted across PubMed, Scopus, and Web of Science for studies published between 2011 and 2024. This review synthesizes findings from 33 peer-reviewed studies to evaluate the diagnostic and prognostic utility of these biomarkers. Results demonstrate that blood Aβ and p-Tau levels strongly correlate with cerebrospinal fluid (CSF) biomarkers and neuroimaging measures of AD pathology. Among the biomarkers analyzed, p-Tau (including p-Tau181 and p-Tau217) consistently exhibited superior diagnostic accuracy, particularly in distinguishing AD from mild cognitive impairment (MCI) and cognitively normal individuals. The combination of Aβ and p-Tau biomarkers further improved diagnostic precision, supporting their complementary roles in AD pathology detection. Despite promising findings, significant heterogeneity among studies underscores the need for assay standardization, validation in diverse populations, and longitudinal research to establish clinical utility. This study concludes that blood-based Aβ and p-Tau biomarkers represent a significant advance in AD diagnostics, offering non-invasive, cost-effective, and scalable solutions for early detection and therapeutic monitoring.