Serum total tau, neurofilament light, and glial fibrillary acidic protein are associated with overall and cardiovascular mortality in a biracial longitudinal population‐based cohort

Abstract Background Serum cytoskeletal biomarkers may indicate greater risk of poor outcomes in age‐related conditions, including mortality. Total tau (t‐tau), neurofilament light (Nf‐L) and glial fibrillary acidic protein (GFAP) are neuronal cytoskeletal biomarkers that are measurable in biofluids. Our objective is to examine separate and combined associations of serum t‐tau, Nf‐L, and GFAP with overall and cardiovascular mortality in a biracial population‐based sample. Method Data came from 1,327 older participants who were either of Black or White racial background from the Chicago Health and Aging Project (CHAP), a longitudinal population‐based study of chronic conditions of aging. An ultrasensitive immunoassay was used to measure the concentration of t‐tau, Nf‐L, and GFAP in blood serum. Mortality based on age at death included overall mortality and cardiovascular mortality. A series of Cox proportional hazard regression models were used to examine associations between biomarker(s) and outcomes (overall and cardiovascular mortality), adjusting for age, gender, education, the APOE‐e4 allele, global cognitive function, and physical functioning. Result In univariate models, 5‐fold higher concentrations of serum t‐tau (HR = 1.46, 95% CI: 1.28, 1.68), Nf‐L (HR = 2.14, 95% CI: 1.79, 2.57), and GFAP (HR = 1.39, 95% CI: 1.07, 1.81) were separately associated with increased risk of overall mortality, with higher risk in participants of Black race versus White in models with t‐tau or Nf‐L. In combined models with all three biomarkers, t‐tau (HR = 1.38, 95% CI: 1.09, 1.75) and Nf‐L (HR = 3.05, 95% CI: 2.35, 3.95) were associated with risk of overall mortality, with racial differences in t‐tau only. In univariate models, higher concentrations of t‐tau (HR = 1.32, 95% CI: 1.03, 1.68), Nf‐L (HR = 2.11, 95% CI: 1.56, 2.88), and GFAP (HR = 1.74, 95% CI: 1.13, 2.69) were separately associated with risk of cardiovascular mortality, with racial differences in t‐tau or Nf‐L. In combined models, only Nf‐L was associated with cardiovascular mortality (HR = 2.84, 95% CI: 1.84, 4.38). Conclusion Serum t‐tau, Nf‐L, and GFAP were associated with increased risk of overall and cardiovascular mortality, with racial differences among associations, in a biracial population‐based sample. Our findings suggest that serum t‐tau, Nf‐L, and GFAP may serve as a potential biomarker for overall and cardiovascular mortality among older adults.