Cross-cultural validation of plasma p-tau217 and p-tau181 as precision biomarkers for amyloid PET positivity: An East Asian study in Taiwan and Korea

Abstract

Introduction: Plasma phosphorylated tau (p-tau) biomarkers have improved Alzheimer's disease (AD) diagnosis, but data from diverse Asian populations are limited. This study evaluated plasma p-tau217 and p-tau181 levels in Korean and Taiwanese populations.

Methods: All participants (n = 270) underwent amyloid positron emission tomography (PET) and blood tests. Plasma p-tau model-derived probabilities of amyloid PET positivity (amyloid beta [Aβ]+) classified participants into low-, intermediate-, or high-risk groups.

Results: In both cohorts, plasma p-tau217 outperformed p-tau181, especially in cognitively unimpaired participants (area under the curve = 0.921 [p-tau217] vs. 0.769 [p-tau181], P_difference = 0.022). Including apolipoprotein E status and glial fibrillary acidic protein improved model fit. The negative predictive value of the low-risk group and positive predictive value of the high-risk group were 97.5% and 86.0%, respectively.

Discussion: Plasma p-tau217 and p-tau181 effectively predict Aβ+ among culturally different Asian populations. P-tau217 performed better, especially in the early stages of AD. Plasma p-tau217-based models reduced intermediate-risk classifications, suggesting fewer amyloid PET scans needed to confirm the diagnosis.

Highlights: The efficacy of plasma phosphorylated tau (p-tau)217 and p-tau181 was analyzed in two Asian populations. Plasma p-tau217 performs better in predicting amyloid positron emission tomography positivity, especially in cognitively unimpaired subjects. Adding apolipoprotein E and glial fibrillary acidic protein to p-tau improved model accuracy. The models from each cohort were confirmed in the other cohort. Plasma p-tau-based risk stratification may reduce the need for confirmatory tests.

Keywords: Alzheimer's disease; amyloid positron emission tomography; apolipoprotein E; glial fibrillary acidic protein; phosphorylated tau181; phosphorylated tau217.