A genetic and proteomic comparison of key AD biomarkers across tissues
Marsh, Thomas W. (Washington University in St. Louis)
Western, Daniel (Washington University in St. Louis)
Timsina, Jigyasha (Washington University in St. Louis)
Gorijala, Priyanka (Washington University in St. Louis)
Yang, Chengran (Washington University in St. Louis)
Pastor, Pau (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Liu, Menghan (Washington University in St. Louis)
Morris, John C. (Washington University in St. Louis)
Bateman, Randall J. (Washington University in St. Louis)
Schindler, Suzanne E. (Washington University in St. Louis)
Sung, Yun Ju (Washington University in St. Louis)
Cruchaga, Carlos (Washington University in St. Louis)
Universitat Autònoma de Barcelona

Date:	2024
Abstract:	INTRODUCTION: Plasma has been proposed as an alternative to cerebrospinal fluid (CSF) for measuring Alzheimer's disease (AD) biomarkers, but no studies have analyzed in detail which biofluid is more informative for genetics studies of AD. METHOD: Eleven proteins associated with AD (α-synuclein, apolipoprotein E [apoE], CLU, GFAP, GRN, NfL, NRGN, SNAP-25, TREM2, VILIP-1, YKL-40) were assessed in plasma (n = 2317) and CSF (n = 3107). Both plasma and CSF genome-wide association study (GWAS) analyses were performed for each protein, followed by functional annotation. Additional characterization for each biomarker included calculation of correlations and predictive power. RESULTS: Eighteen plasma protein quantitative train loci (pQTLs) associated with 10 proteins and 16 CSF pQTLs associated with 9 proteins were identified. Plasma and CSF shared some genetic loci, but protein levels between tissues correlated weakly. CSF protein levels better associated with AD compared to plasma. DISCUSSION: The present results indicate that CSF is more informative than plasma for genetic studies in AD. Highlights: The identification of novel protein quantitative trait loci (pQTLs) in both plasma and cerebrospinal fluid (CSF). Plasma and CSF levels of neurodegeneration-related proteins correlated weakly. CSF is more informative than plasma for genetic studies of Alzheimer's disease (AD). Neurofilament light (NfL), triggering receptor expressed on myeloid cells 2 (TREM2), and chitinase-3-like protein 1 (YKL-40) tend to show relatively strong inter-tissue associations. A novel signal in the apolipoprotein E (APOE) region was identified, which is an eQTL for APOC1.
Grants:	Agencia Estatal de Investigación PID2020-115613RA-I00
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Alzheimer's disease ; CSF ; Biomarkers ; Genomics ; Neurodegenerative disease ; Plasma ; Protein quantitative trait loci
Published in:	Alzheimer's & dementia, Vol. 20 Núm. 9 (september 2024) , p. 6423-6440, ISSN 1552-5279

DOI: 10.1002/alz.14139
PMID: 39077866

18 p, 4.2 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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