Plasma phosphorylated tau (p-tau) and β-amyloid (Aβ) are promising biomarkers for Alzheimer’s disease (AD). However, it remains unclear whether combining p-tau with Aβ provides better predictive performance than using p-tau alone.

To evaluate the predictive utility of plasma p-tau and Aβ combinations for AD-related pathology, brain atrophy, and cognitive decline.

This study included 352 participants from the Greater-Bay Area Healthy Aging Brain Study (GHABS) cohort in China, classified into 227 Aβ-negative and 125 Aβ-positive individuals.

Participants underwent Aβ positron emission tomography (PET) and plasma biomarker assessments. Plasma concentrations of p-tau181, p-tau217, p-tau231, Aβ42, and Aβ40 were quantified on the Quanterix HD-X and Lumipulse G1200 platform.

Among the individual plasma p-tau variants, p-tau217 consistently outperformed p-tau181 and p-tau231. The combination of p-tau biomarkers (p-tau181, p-tau217, and p-tau231) with Aβ42 or the Aβ42/40 ratio further improved discrimination between Aβ+/CU (cognitively unimpaired) and Aβ-/CU individuals. Both p-tau/Aβ42 and p-tau/(Aβ42/40) exhibited slightly stronger or comparable associations with Aβ PET burden, baseline and longitudinal measures of hippocampal atrophy, AD-typical cortical thinning, and cognitive decline, relative to p-tau alone.

The head-to-head comparisons indicate that p-tau217 is the most robust biomarker among the variants tested, and p-tau/Aβ ratios perform comparably or slightly better than p-tau alone in reflecting AD pathology, potentially providing complementary information for early detection and monitoring of disease progression.