Plasma biomarkers have been recommended for Alzheimer's disease (AD) diagnosis. However, the age-dependent trajectories and potential nonlinear associations between age and plasma biomarkers remain incompletely characterized among cognitively normal adults. 

Methods

This was a population based cross-sectional study, and 780 cognitively normal adults aged 40 years or older were enrolled. The mean age was 58.14 ± 9.05 years (range: 40-85 years), with 305 men (39.0%). Plasma levels of phosphorylated tau 217 (p-tau217), phosphorylated tau 181 (p-tau181), amyloid-β42/40 ratio (Aβ42/40), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) were quantified using electrochemiluminescence assays. Correlation analyses and multivariable linear regression models were used to investigate the relationship between age and plasma biomarkers.

Plasma concentrations of GFAP, NfL, p-tau181, and p-tau217 increased progressively with advancing age, whereas the Aβ42/40 showed a decreasing trend. Pearson correlation analyses demonstrated positive correlations between age and p-tau217 (ρ=0.145), p-tau181 (ρ=0.190), GFAP (ρ=0.496), and NfL (ρ=0.593), while Aβ42/40 was negatively correlated with age (ρ=-0.157) (all P<0.001). In fully adjusted multivariable linear regression models, older age remained independently associated with higher levels of GFAP, NfL, p-tau181, and p-tau217, and with a lower Aβ42/40 (all P<0.05). RCS analyses revealed no statistically significant nonlinear associations for any biomarker (all Pₙₒₙₗᵢₙₑₐᵣ>0.05), indicating predominantly linear relationships between age and plasma biomarker levels across the age spectrum.

Plasma levels of p-tau181, p-tau217, GFAP, NfL increase with aging, while Aβ42/40 decrease with aging significantly. These indicated that plasma biomarkers levels associated with aging strongly. It may be necessary to determine an age-specific cutoff value of plasma biomarkers in AD diagnosis.