Dage, Jeffrey L; Eloyan, Ani; Thangarajah, Maryanne; Hammers, Dustin B; Fagan, Anne M; Gray, Julia D; Schindler, Suzanne E; Snoddy, Casey; Nudelman, Kelly NH; Faber, Kelley M; Foroud, Tatiana; Aisen, Paul; Griffin, Percy; Grinberg, Lea T; Iaccarino, Leonardo; Kirby, Kala; Kramer, Joel; Koeppe, Robert; Kukull, Walter A; La Joie, Renaud; Mundada, Nidhi S; Murray, Melissa E; Rumbaugh, Malia; Soleimani‐Meigooni, David N; Toga, Arthur W; Touroutoglou, Alexandra; Vemuri, Prashanthi; Atri, Alireza; Beckett, Laurel A; Day, Gregory S; Graff‐Radford, Neill R; Duara, Ranjan; Honig, Lawrence S; Jones, David T; Masdeu, Joseph C; Mendez, Mario F; Musiek, Erik; Onyike, Chiadi U; Riddle, Meghan; Rogalski, Emily; Salloway, Stephen; Sha, Sharon J; Turner, Raymond S; Wingo, Thomas S; Wolk, David A; Womack, Kyle B; Carrillo, Maria C; Dickerson, Bradford C; Rabinovici, Gil D; Apostolova, Liana G; Consortium, LEADS

doi:10.1002/alz.13399

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

2023

Published Web Location

https://doi.org/10.1002/alz.13399

Abstract

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.

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