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A genetic and proteomic comparison of key AD biomarkers across tissues.
Marsh, Thomas W; Western, Daniel; Timsina, Jigyasha; Gorijala, Priyanka; Yang, Chengran; Pastor, Pau; Liu, Menghan; Morris, John C; Bateman, Randall J; Schindler, Suzanne E; Sung, Yun Ju; Cruchaga, Carlos.
Afiliación
  • Marsh TW; Division of Biology & Biomedical Sciences, Washington University in St. Louis, St. Louis, Missouri, USA.
  • Western D; Department of Psychiatry, Washington University in St. Louis, St. Louis, Missouri, USA.
  • Timsina J; Neurogenomics and Informatics, Washington University in St. Louis, St. Louis, Missouri, USA.
  • Gorijala P; Division of Biology & Biomedical Sciences, Washington University in St. Louis, St. Louis, Missouri, USA.
  • Yang C; Department of Psychiatry, Washington University in St. Louis, St. Louis, Missouri, USA.
  • Pastor P; Neurogenomics and Informatics, Washington University in St. Louis, St. Louis, Missouri, USA.
  • Liu M; Department of Psychiatry, Washington University in St. Louis, St. Louis, Missouri, USA.
  • Morris JC; Neurogenomics and Informatics, Washington University in St. Louis, St. Louis, Missouri, USA.
  • Bateman RJ; Division of Biology & Biomedical Sciences, Washington University in St. Louis, St. Louis, Missouri, USA.
  • Schindler SE; Department of Psychiatry, Washington University in St. Louis, St. Louis, Missouri, USA.
  • Sung YJ; Department of Psychiatry, Washington University in St. Louis, St. Louis, Missouri, USA.
  • Cruchaga C; Unit of Neurodegenerative diseases, Department of Neurology, University Hospital Germans Trias i Pujol and The Germans Trias i Pujol Research Institute (IGTP) Badalona, Barcelona, Spain.
Alzheimers Dement ; 20(9): 6423-6440, 2024 Sep.
Article en En | MEDLINE | ID: mdl-39077866
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Biomarcadores / Proteómica / Estudio de Asociación del Genoma Completo / Enfermedad de Alzheimer Límite: Aged / Female / Humans / Male Idioma: En Revista: Alzheimers Dement Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Biomarcadores / Proteómica / Estudio de Asociación del Genoma Completo / Enfermedad de Alzheimer Límite: Aged / Female / Humans / Male Idioma: En Revista: Alzheimers Dement Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos