In this study, we established the thresholds for plasma Aβ42/Aβ40 and plasma p-Tau181 and demonstrated that individuals positive for these biomarkers (A+/T+) exhibited the most significant alterations in plasma GFAP, Aβ PET, tau PET, plasma NfL, hippocampal volume, and AD-signature cortical thickness within a Chinese community-based aging cohort. The gene discussed is MAPT; the disease is Alzheimer disease.