Blood phosphorylated Tau181 reliably differentiates amyloid-positive from amyloid-negative subjects in the Alzheimer's disease continuum: A systematic review and meta-analysis

Alzheimers Dement (Amst). 2025 Jan 16;17(1):e70068. doi: 10.1002/dad2.70068. eCollection 2025 Jan-Mar.

Abstract

Introduction: Blood-based biomarkers seem promising for the diagnosis of Alzheimer's disease (AD).

Methods: We performed a systematic review and meta-analysis on the potential of blood phosphorylated Tau181 (p-tau181) to differentiate amyloid-positive (A+) and amyloid-negative (A-) subjects. Two meta-analyses were conducted, showing the mean p-tau values in blood and cerebrospinal fluid (CSF) in the A+ and A- group, and the second comparing the mean p-tau concentrations in blood and CSF among A+ versus A- participants, by laboratory assessment method.

Results: Eighteen studies (2764 A+ and 5646 A- subjects) were included. The single-group meta-analysis showed mean higher blood p-tau181 values in the A+ than in the A- group. In the head-to-head meta-analysis, blood p-tau reliably differentiated A+ patients from A- participants.

Discussion: Regardless of the laboratory technique, blood p-tau181 reliably differentiates A+ and A- subjects. Therefore, it might have important applications for early diagnosis and inclusion in clinical trials for AD patients.

Highlights: The role of blood-based biomarkers in discriminating AD patients is still uncertain.Blood p-tau181 distinguishes among amyloid-positive and amyloid-negative subjects.Blood p-tau181 might allow early diagnosis and inclusion in clinical trials.

Keywords: Alzheimer's disease (AD); CSF; biomarkers; blood; meta‐analysis; phosphorylated Tau181 (p‐tau181).

Publication types

  • Review