Combining plasma p-tau₂₃₁ and glial fibrillary acidic protein produces higher discriminative accuracy for amyloid positivity than other blood-based biomarker combinations

Alzheimers Dement. 2025 Oct;21(10):e70796. doi: 10.1002/alz.70796.

ABSTRACT

INTRODUCTION: Plasma phosphorylated tau₂₃₁ (p-tau₂₃₁) has shown great promise for early identification of amyloid pathology. We tested various plasma biomarker combinations with p-tau231 in relation to cerebrospinal fluid (CSF) amyloid positivity.

METHODS: One hundred and fifty-five dementia-free older adults were included. Plasma p-tau231, glial fibrillary acidic protein (GFAP), β-amyloid42/40, and neurofilament light chain (NfL) were related to amyloid positivity via logistic regression. Subsequent models assessing various combinations of biomarkers were compared to a base model containing only p-tau₂₃₁.

RESULTS: In single predictor models, p-tau231 (AUC = 0.87, p = 0.005) and GFAP (AUC = 0.87, p = 0.01) were associated with amyloid positivity, and p-tau231 remained significant in all multi-predictor models (p-values < 0.02). In comparison to the base model with p-tau231 only, models adding GFAP improved the prediction of amyloid positivity (p < 0.03).

DISCUSSION: Plasma p-tau231 and GFAP were associated with amyloid positivity. Models including both p-tau231 and GFAP performed best, while including β-amyloid42/40 and NfL did not produce a better fitting model.

HIGHLIGHTS: Plasma p-tau231 and glial fibrillary acidic protein (GFAP) are accurate predictors of amyloid positivity. Combining plasma p-tau231 and GFAP improves accuracy. Adding other biomarkers beyond p-tau231 and GFAP does not improve models.

PMID:41065027 | DOI:10.1002/alz.70796