Potential utility of plasma pTau217 for assessing amyloid and tau biomarker profiles

Eur J Nucl Med Mol Imaging. 2025 Aug 6. doi: 10.1007/s00259-025-07457-y. Online ahead of print.

ABSTRACT

PURPOSE: Plasma phosphorylated tau 217 (pTau217) is a promising biomarker for Alzheimer's disease, reflecting both amyloid β (Aβ) and tau positron emission tomography (PET) results. While its diagnostic role is actively being investigated, this study aims to expand its application to staging disease progression and predicting cognitive decline.

METHODS: A total of 2,919 participants, primarily diagnosed as Alzheimer's clinical syndrome, were recruited. Plasma pTau217 was measured using the ALZpath assay, and its diagnostic accuracy for binary Aβ/tau (A/T) biomarker profiles and Aβ and tau PET staging was assessed using area under the curve (AUC). Longitudinal Mini-Mental State Examination (MMSE) changes according to plasma pTau217-based staging were analyzed.

RESULTS: Plasma pTau217 accurately predicted binary Aβ (AUC 0.96) and tau (AUC 0.90) PET positivity. Both the Aβ-positive/tau-positive (A_ptau+/T_ptau+) and Aβ-positive/tau-negative (A_ptau+/T_ptau-) groups, defined using plasma pTau217 cutoffs, showed significantly worse MMSE trajectories compared to the Aβ-negative/tau-negative (A_ptau-/T_ptau-) group (for A_ptau+/T_ptau+ vs. A_ptau-/T_ptau-, β = -1.061 ± 0.055; for A_ptau+/T_ptau- vs. A_ptau-/T_ptau-, β = -0.322 ± 0.070, all adjusted P < 0.001). However, its performance was less effective for Aβ and tau PET staging, particularly for medial temporal tau PET stage (AUC 0.71). Nevertheless, plasma pTau217-based staging distinguished longitudinal MMSE deterioration (all adjusted P < 0.001).

CONCLUSION: Plasma pTau217 is effective for predicting A/T biomarker profile and cognitive decline, though further study is needed to better explain its association with Aβ and tau PET staging.

CLINICAL TRIAL NUMBER: Not applicable.

PMID:40768095 | DOI:10.1007/s00259-025-07457-y