Longitudinal Changes in Blood Biomarkers of Clinical Alzheimer Disease in a Biracial Population Sample

Background and Objectives: Recent studies suggest the utility of blood biomarkers in detecting changes in neurodegenerative disorders. The objective of our research is to test the hypothesis that the longitudinal changes in total tau (t-tau), neurofilament light (Nf-L), and glial fibrillary acidic protein (GFAP) is associated with structural MRI and the development of clinical Alzheimer’s disease (AD), and cognitive decline.

Methods: Data came from a population-based sample with serum concentrations of t-tau, Nf-L, and GFAP and cognitive characteristics measured over 17 years. The inclusion criteria for this investigation were based on participants with blood samples, cognitive function testing, and clinical diagnosis for AD. The longitudinal changes in the serum biomarkers were examined using linear mixed models for log10 transformed concentrations.

Results: In 1,327 participants (60% Black participants and 60% women, the concentration of t-tau increased annually by 4.8% (95% CI= 4.0, 5.6) and Nf-L by 5.9% (95% CI= 5.4, 6.4). The longitudinal change in GFAP was higher among Black participants than White participants (4.4% vs. 3.5% per year, p=0.028). Baseline MRI characteristics were associated with the longitudinal changes in serum biomarkers of clinical AD. Specifically, a higher baseline third ventricular volume was associated with a higher rate of increase in the concentration of t-tau, and white matter hyperintensities predicted a higher rate of increase in Nf-L. The rate of change in concentrations of t-tau, NF-L, and GFAP was significantly higher among those who developed clinical AD than those with no cognitive impairment. For each standard deviation unit decline in global cognition, longitudinal change in t-tau increased by 81% (95% CI= 76, 86), Nf-L by 113% (95% CI= 105, 120), and GFAP by 66% (95% CI= 62, 70).

Discussion: Blood biomarkers showed significant longitudinal changes corresponding to cognitive decline, clinical AD, and structural MRI characteristics. Our findings show that longitudinal changes in serum biomarkers were associated with several cognitive endophenotypes.

Glossary: t-tau= total tau; Nf-L= Neurofilament Light; GFAP= Glial Fibrillary Acidic Protein; AD= Alzheimer’s disease; MRI= Magnetic Resonance Imaging; CI = Confidence Interval

Classification of Evidence: The study found Class II evidence that longitudinal changes in serum t-tau, Nf-L, and GFAP were associated with cognitive decline and the development of clinical AD in people over age 65.