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

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

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish
Pages (from-to)S115-S125
JournalAlzheimer's and Dementia
Volume19
Issue numberS9
DOIs
StatePublished - Nov 2023

Keywords

  • Alzheimer's disease
  • Aβ42/40
  • CSF
  • NfL
  • SNAP-25
  • VILIP-1
  • YKL-40
  • amyloid
  • astrogliosis
  • biomarkers
  • dementia
  • neurogranin
  • pTau181
  • tTau
  • tau

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