Neurofilament Light Chain as a Key Predictor of Cognitive Function and Mortality in Centenarians: A Study of Plasma Neural Biomarkers in Aging

Blood-based neural biomarkers linked to systemic aging may provide insights into the biological endpoint of human lifespan. However, the key biomarker for predicting cognitive function and survival at extreme ages remains unclear. In this study, the relationship between neural biomarkers amyloid-β42/amyloid-β40 ratio (Aβ42/40), phosphorylated Tau181 (pTau181), and Neurofilament Light Chain (NfL), and cognitive function was examined in 495 centenarians. Longitudinal analysis was also performed on the same cohort. The results showed that NfL, a marker of non-specific axonal injury, was the strongest predictor of Mini-Mental State Examination (MMSE) scores (B [95% CI] = −2.28 [−3.72 – −0.85]) after adjusting for confounders. Higher NfL levels were also associated with increased mortality (HR [95% CI] = 2.82 [1.71 − 4.65]). These findings suggest NfL reflects neurodegeneration linked to late-life biological aging.