Plasma p-tau217, p-tau181, and NfL as early indicators of dementia risk in a community cohort: The Shanghai Aging Study.

Abstract

Blood biomarkers showed values for predicting future cognitive impairment. Evidence from the community-based cohort was limited only in high-income countries. This study included 1857 dementia-free community residents recruited in 2009-2011 and followed up in waves 2014-2016 and 2019-2023 in the Shanghai Aging Study. We intended to explore the relationships of baseline plasma ALZpath phosphorylated tau 217 (p-tau217), p-tau181, neurofilament light chain (NfL) with follow-up incident dementia, Alzheimer's disease (AD), and amyloidosis. Higher concentrations of plasma p-tau217, p-tau181, and NfL were correlated to higher decline speed of Mini-Mental State Examination score, and higher risk of incident dementia and AD. The p-tau217 demonstrated a significant correlation with longitudinal neocortical amyloid-beta (Aβ) deposition (r=0.57 [0.30, 0.76]) and a high accuracy differentiating Aβ+ from Aβ- at follow-ups (area under the receiver operating characteristic curve=0.821 [0.703, 0.940]). Plasma p-tau217 may be an early predictive marker of AD and Aβ pathology in older community-dwelling individuals.Highlights: Plasma p-tau217, p-tau181, and NfL were positively associated with long-term cognitive decline and risk of incident dementia.Plasma p-tau217 showed a better performance distinguishing Aβ+ individuals from Aβ- individuals at follow-ups.Plasma NfL may be a suitable predictor of general cognitive decline in older community-dwelling individuals.