Concordance between plasma biomarkers of phosphorylated tau and tau-PET: A narrative review.

Plasma phosphorylated tau (p-tau) and tau positron emission tomography (PET) are key biomarkers for detecting tau pathology in Alzheimer's disease (AD), offering both diagnostic and prognostic value. However, the concordance between plasma p-tau (p-tau217/p-tau181/p-tau231) positivity and tau-PET positivity remains incompletely understood. In this narrative review, we show that concordance varies by clinical disease stage, the plasma p-tau biomarker assessed, the definition of tau-PET positivity, and the presence of comorbidities and other risk factors. We also present evidence for a temporal sequence of plasma p-tau changes, with plasma p-tau231 positivity preceding p-tau181 positivity, followed by plasma p-tau217 reflecting more advanced stages of tau pathology. We highlight the relevance of these temporal dynamics for the potential development of a stage-specific trajectory framework for plasma p-tau and discuss how such a framework may support improved integration of plasma p-tau and tau-PET, thereby enhancing screening efficiency. Finally, we outline methodological challenges, highlight current efforts such as the development of tau-PET harmonization strategies, and identify priorities for future research. Taken together, this review provides a comprehensive overview of the factors influencing concordance between plasma p-tau positivity and tau-PET positivity. Careful consideration of these factors will be essential for the optimal integration of these biomarkers across the AD spectrum, with the potential to improve both diagnostic and therapeutic strategies.