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 Joie; Nidhi 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; LEADS Consortium

doi:10.1002/alz.13399

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

Alzheimers Dement. 2023 Nov;19 Suppl 9(Suppl 9):S115-S125. doi: 10.1002/alz.13399. Epub 2023 Jul 25.

Authors

Jeffrey L Dage^{1

2}, Ani Eloyan³, Maryanne Thangarajah³, Dustin B Hammers¹, Anne M Fagan⁴, Julia D Gray⁴, Suzanne E Schindler⁴, Casey Snoddy², Kelly N H Nudelman², Kelley M Faber², Tatiana Foroud², Paul Aisen⁵, Percy Griffin⁶, Lea T Grinberg^{7

8}, Leonardo Iaccarino⁷, Kala Kirby¹, Joel Kramer⁷, Robert Koeppe⁹, Walter A Kukull¹⁰, Renaud La Joie⁷, Nidhi S Mundada⁷, Melissa E Murray¹¹, Malia Rumbaugh², David N Soleimani-Meigooni⁷, Arthur W Toga¹², Alexandra Touroutoglou¹³, Prashanthi Vemuri¹⁴, Alireza Atri¹⁵, Laurel A Beckett¹⁶, Gregory S Day¹⁷, Neill R Graff-Radford¹⁷, Ranjan Duara¹⁸, Lawrence S Honig¹⁹, David T Jones^{14

20}, Joseph C Masdeu²¹, Mario F Mendez²², Erik Musiek⁴, Chiadi U Onyike²³, Meghan Riddle²⁴, Emily Rogalski²⁵, Stephen Salloway²⁴, Sharon J Sha²⁶, Raymond S Turner²⁷, Thomas S Wingo²⁸, David A Wolk²⁹, Kyle B Womack⁴, Maria C Carrillo⁶, Bradford C Dickerson¹³, Gil D Rabinovici⁷, Liana G Apostolova^{1

5

30}; LEADS Consortium

Affiliations

¹ Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
² Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
³ Department of Biostatistics, Center for Statistical Sciences, Brown University, Providence, Rhode Island, USA.
⁴ Department of Neurology, Washington University in St. Louis, St. Louis, Missouri, USA.
⁵ Alzheimer's Therapeutic Research Institute, University of Southern California, San Diego, California, USA.
⁶ Medical & Scientific Relations Division, Alzheimer's Association, Chicago, Illinois, USA.
⁷ Department of Neurology, University of California - San Francisco, San Francisco, California, USA.
⁸ Department of Pathology, University of California - San Francisco, San Francisco, California, USA.
⁹ Department of Radiology, University of Michigan, Ann Arbor, Michigan, USA.
¹⁰ Department of Epidemiology, University of Washington, Seattle, Washington, USA.
¹¹ Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
¹² Laboratory of Neuro Imaging, USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, Los Angeles, California, USA.
¹³ Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
¹⁴ Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
¹⁵ Banner Sun Health Research Institute, Sun City, Arizona, USA.
¹⁶ Department of Public Health Sciences, University of California-Davis, Davis, California, USA.
¹⁷ Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA.
¹⁸ Wien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center, Miami, Florida, USA.
¹⁹ Taub Institute and Department of Neurology, Columbia University Irving Medical Center, New York, New York, USA.
²⁰ Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
²¹ Nantz National Alzheimer Center, Houston Methodist and Weill Cornell Medicine, Houston, Texas, USA.
²² Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
²³ Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
²⁴ Department of Neurology, Alpert Medical School, Brown University, Providence, Rhode Island, USA.
²⁵ Department of Psychiatry and Behavioral Sciences, Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
²⁶ Department of Neurology & Neurological Sciences, Stanford University, Palo Alto, California, USA.
²⁷ Department of Neurology, Georgetown University, Washington, D.C., USA.
²⁸ Department of Neurology and Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA.
²⁹ Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
³⁰ Department of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine Indianapolis, Indianapolis, Indiana, USA.

PMID: 37491668
PMCID: PMC10877673 (available on 2024-11-01)
DOI: 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.

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

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Alzheimer Disease* / cerebrospinal fluid
Alzheimer Disease* / diagnosis
Amyloid beta-Peptides / cerebrospinal fluid
Biomarkers / cerebrospinal fluid
Chitinase-3-Like Protein 1
Humans
Longitudinal Studies
Neurogranin / cerebrospinal fluid
tau Proteins / cerebrospinal fluid

Substances

Chitinase-3-Like Protein 1
Amyloid beta-Peptides
tau Proteins
Biomarkers
Neurogranin

Abstract

Publication types

MeSH terms

Substances

Grants and funding