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

Abstract

INTRODUCTION: Blood biomarkers showed values for predicting future cognitive impairment. Evidence from the community-based cohort was limited only in high-income countries. METHODS: 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. RESULTS: 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]). DISCUSSION: 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.