Diurnal fluctuation of plasma Alzheimer’s disease biomarkers in healthy young Chinese adults

Abstract

Plasma amyloid-β (Aβ) and phosphorylated tau (P-tau) are becoming biomarkers for Alzheimer’s disease (AD) diagnosis. However, the variation of plasma levels among different sampling times remains underexplored. In this study, we investigated the diurnal fluctuation of plasma biomarkers in healthy adults. Nineteen healthy adults (average age 29.95 ± 4.81 years, 47.4% female) underwent ethylenediamine tetraacetic acid (EDTA) plasma sampling around timepoints 08:00, 12:00 and 16:00—approximately 30 to 60 min before they consumed meals—on two consecutive days. All participants had normal sleep as usual during the experiment. Plasma Aβ 42 , Aβ 40 , P-tau181, P-tau217, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) concentrations were measured using chemiluminescence immunoassay method. Linear mixed models assessed timepoint effects and associations with hours since wake. Plasma P-tau181 levels at 12:00 increased by 14.8% (mean difference = 0.239 pg/mL, 95% CI [0.027, 0.451], P = 0.022) compared to that at 08:00, and the levels at 16:00 increased by 25.1% (mean difference = 0.460 pg/mL, 95% CI [0.247, 0.673], P < 0.001) than that at 08:00. Plasma P-tau217 also exhibited significant daytime increase (16:00 vs. 08:00, + 12.8%, mean difference = 0.209 pg/mL, 95% CI [0.029, 0.389], P = 0.017). Meanwhile, plasma P-tau levels were positively correlated with wake duration (P-tau181: r = 0.3500, P < 0.001; P-tau217: r = 0.1946, P = 0.007). Plasma Aβ 42 , Aβ 40 , GFAP, NfL, and Aβ 42 /Aβ 40 remained stable across all timepoints. Blood sampling time may warrant consideration when using plasma AD biomarkers in clinical research settings and longitudinal monitoring, pending validation in larger, independent cohorts.