Remote Blood Biomarkers of Longitudinal Cognitive Outcomes in a Population Study.

Objective The longitudinal association of blood biomarkers of total tau (t-tau), neurofilament light (Nf-L), and glial fibrillary acidic protein (GFAP) with common sporadic AD and cognitive decline are not established. Methods Using a single molecule array technology, ultrasensitive immunoassays for serum concentrations of total tau (t-tau), neurofilament light (Nf-L), and glial fibrillary acidic protein (GFAP) were measured in a population sample of 1,327 participants (60% African Americans and women) who had a clinical evaluation for AD, completed in-home cognitive assessments, and undergone 1.5T structural MRI. Results Higher concentrations of serum biomarkers were associated with the development of clinical AD, especially, the time-specific associations were notable: t-tau 8-16 years, and Nf-L and GFAP 4-8 years prior to clinical AD. Serum biomarkers were associated with faster cognitive decline over 16 years: baseline t-tau above 0.40 pg/mL had 30% faster decline, Nf-L above 25.5 pg/mL had 110% faster decline, and GFAP above 232 pg/mL had 130% faster decline compared to those in the lowest quartile. Participants with baseline GFAP above 232 pg/mL showed 160% faster decline in hippocampal volume compared to those below 160 pg/mL. Additionally, higher baseline t-tau was associated with faster increase in third ventricular volume, and baseline Nf-L and GFAP were associated with faster decline in cortical thickness. Interpretation Serum t-tau, Nf-L, and GFAP predict the development of sporadic AD and cognitive decline, and changes in structural brain characteristics, suggesting their usefulness not only as screening and predictive biomarkers, but also in capturing the pathogenesis of Alzheimer's dementia This article is protected by copyright. All rights reserved.