Blood-Based Tau as a Biomarker for Early Detection and Monitoring of Alzheimer's Disease: A Systematic Review and Meta-Analysis.

Alzheimer's disease (AD), the most prevalent form of dementia, is a progressive neurodegenerative disorder characterized by cognitive decline and memory loss, ultimately leading to loss of independence and reduced quality of life. Since current treatments are most effective in early stages, the development of reliable and noninvasive biomarkers for early diagnosis and monitoring is crucial. Abnormal tau protein aggregation is a key pathological hallmark of AD, disrupting neuronal integrity, accelerating progression, and associating closely with cognitive decline and the transition to mild cognitive impairment, a prodromal stage of AD. Currently, tau pathology is evaluated mainly by cerebrospinal fluid analysis and tau positron emission tomography (tau PET), which are invasive or costly, limiting their clinical applicability. This systematic review and meta-analysis synthesized evidence on tau as a blood-based biomarker for dementia, with emphasis on its relationship to tau PET, the gold standard for in vivo tau assessment. Findings indicate that elevated plasma tau levels such as p-tau181, p-tau217 and p-tau231 consistently reflect brain tau pathology, supporting their role as surrogate markers. Large-scale longitudinal validation is warranted to establish blood-based tau as a practical, accessible tool for early detection and disease monitoring, thereby improving therapeutic outcomes in AD.