Plasma p-Tau217 and Aβ42/40 for identifying amyloid PET positivity in cognitively unimpaired asian individuals: A systematic review and meta-analysis.

BACKGROUND: Blood-based biomarkers have emerged as promising tools for detecting Alzheimer disease (AD) pathology, but their performance in cognitively unimpaired Asian populations remains unclear. METHODS: We conducted a systematic review and random-effects meta-analysis to evaluate the ability of plasma p-tau217, Aβ42/40, and composite biomarkers to discriminate amyloid-β positron emission tomography (Aβ PET) positivity in cognitively unimpaired Asian populations. CENTRAL, PubMed, and CINAHL were systematically searched. The primary analysis pooled the area under the curve (AUC) for p-tau217 and Aβ42/40 separately to evaluate discrimination of Aβ PET positivity. Secondary analyses examined standardized mean differences (SMDs) in biomarker levels between Aβ PET-positive and Aβ PET-negative groups for p-tau217 and Aβ42/40, and additionally pooled AUCs for composite biomarkers, including p-tau217/Aβ42 and combined p-tau217 and Aβ42/40 models. RESULTS: Nine studies comprising 11 analyzable datasets and 2566 cognitively unimpaired participants were included. The pooled AUC was 0.88 for plasma p-tau217 and 0.86 for plasma Aβ42/40. In secondary analyses, the pooled SMD between Aβ PET-positive and Aβ PET-negative individuals was 2.28 for p-tau217 and -1.17 for Aβ42/40. Composite biomarkers showed higher discriminative performance, with pooled AUCs of 0.920 for p-tau217/Aβ42 and 0.924 for combined p-tau217 and Aβ42/40 models. CONCLUSIONS: In cognitively unimpaired Asian populations, plasma p-tau217 and Aβ42/40 showed good discriminative performance for Aβ PET positivity. Further standardization, external validation, and prospective evaluation are needed.