Cerebrospinal fluid biomarkers in the Longitudinal Early-onset Alzheimer's Disease Study.

Introduction: One goal of the Longitudinal Early Onset Alzheimer's Disease Study (LEADS) is to define the fluid biomarker characteristics of early-onset Alzheimer's disease (EOAD).

Methods: Cerebrospinal fluid (CSF) concentrations of Aβ1-40, Aβ1-42, total tau (tTau), pTau181, VILIP-1, SNAP-25, neurogranin (Ng), neurofilament light chain (NfL), and YKL-40 were measured by immunoassay in 165 LEADS participants. The associations of biomarker concentrations with diagnostic group and standard cognitive tests were evaluated.

Results: Biomarkers were correlated with one another. Levels of CSF Aβ42/40, pTau181, tTau, SNAP-25, and Ng in EOAD differed significantly from cognitively normal and early-onset non-AD dementia; NfL, YKL-40, and VILIP-1 did not. Across groups, all biomarkers except SNAP-25 were correlated with cognition. Within the EOAD group, Aβ42/40, NfL, Ng, and SNAP-25 were correlated with at least one cognitive measure. Discussion: This study provides a comprehensive analysis of CSF biomarkers in sporadic EOAD that can inform EOAD clinical trial design.