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Large-scale network analysis of the cerebrospinal fluid proteome identifies molecular signatures of frontotemporal lobar degeneration.
Saloner, Rowan; Staffaroni, Adam; Dammer, Eric; Johnson, Erik C B; Paolillo, Emily; Wise, Amy; Heuer, Hilary; Forsberg, Leah; Lago, Argentina Lario; Webb, Julia; Vogel, Jacob; Santillo, Alexander; Hansson, Oskar; Kramer, Joel; Miller, Bruce; Li, Jingyao; Loureiro, Joseph; Sivasankaran, Rajeev; Worringer, Kathleen; Seyfried, Nicholas; Yokoyama, Jennifer; Seeley, William; Spina, Salvatore; Grinberg, Lea; VandeVrede, Lawren; Ljubenkov, Peter; Bayram, Ece; Bozoki, Andrea; Brushaber, Danielle; Considine, Ciaran; Day, Gregory; Dickerson, Bradford; Domoto-Reilly, Kimiko; Faber, Kelley; Galasko, Douglas; Geschwind, Daniel; Ghoshal, Nupur; Graff-Radford, Neill; Hales, Chadwick; Honig, Lawrence; Hsiung, Ging-Yuek; Huey, Edward; Kornak, John; Kremers, Walter; Lapid, Maria; Lee, Suzee; Litvan, Irene; McMillan, Corey; Mendez, Mario; Miyagawa, Toji.
Afiliación
  • Saloner R; University of California, San Francisco.
  • Staffaroni A; University of California, San Francisco.
  • Dammer E; Emory University.
  • Johnson ECB; Emory University School of Medicine.
  • Paolillo E; University of California, San Francisco.
  • Wise A; University of California, San Francisco.
  • Heuer H; University of California, San Francisco.
  • Forsberg L; Mayo Clinic.
  • Lago AL; University of California, San Francisco.
  • Webb J; University of California, San Francisco.
  • Vogel J; Lund University.
  • Santillo A; Lund University.
  • Hansson O; Lund University.
  • Kramer J; University of California, San Francisco.
  • Miller B; University of California San Francisco.
  • Li J; Novartis Institutes for Biomedical Research, Inc.
  • Sivasankaran R; Novartis Institutes for Biomedical Research.
  • Worringer K; Novartis (United States).
  • Seyfried N; Emory University School of Medicine.
  • Yokoyama J; UCSF.
  • Seeley W; University of California at San Francisco.
  • Spina S; University of California, San Francisco.
  • Grinberg L; University of California at San Francisco.
  • VandeVrede L; University of California, San Francisco.
  • Ljubenkov P; University of California, San Francisco.
  • Bayram E; University of California, San Diego.
  • Bozoki A; University of North Carolina.
  • Brushaber D; Mayo Clinic.
  • Considine C; Vanderbilt University.
  • Day G; Mayo Clinic in Florida.
  • Dickerson B; Harvard University.
  • Domoto-Reilly K; University of Washington.
  • Faber K; Indiana University.
  • Galasko D; UC San Diego.
  • Geschwind D; UCLA Health System and David Geffen School of Medicine.
  • Ghoshal N; Washington University.
  • Graff-Radford N; Mayo Clinic.
  • Hales C; Emory University.
  • Honig L; Columbia University.
  • Hsiung GY; University of British Columbia.
  • Huey E; Columbia University.
  • Kornak J; University of California, San Francisco.
  • Kremers W; Mayo Clinic.
  • Lapid M; Mayo Clinic.
  • Lee S; University of California, San Francisco.
  • Litvan I; UCSD.
  • McMillan C; Department of Neurology, University of Pennsylvania, Philadelphia, USA.
  • Miyagawa T; Mayo Clinic.
Res Sq ; 2024 Mar 28.
Article en En | MEDLINE | ID: mdl-38585969
ABSTRACT
The pathophysiological mechanisms driving disease progression of frontotemporal lobar degeneration (FTLD) and corresponding biomarkers are not fully understood. We leveraged aptamer-based proteomics (> 4,000 proteins) to identify dysregulated communities of co-expressed cerebrospinal fluid proteins in 116 adults carrying autosomal dominant FTLD mutations (C9orf72, GRN, MAPT) compared to 39 noncarrier controls. Network analysis identified 31 protein co-expression modules. Proteomic signatures of genetic FTLD clinical severity included increased abundance of RNA splicing (particularly in C9orf72 and GRN) and extracellular matrix (particularly in MAPT) modules, as well as decreased abundance of synaptic/neuronal and autophagy modules. The generalizability of genetic FTLD proteomic signatures was tested and confirmed in independent cohorts of 1) sporadic progressive supranuclear palsy-Richardson syndrome and 2) frontotemporal dementia spectrum syndromes. Network-based proteomics hold promise for identifying replicable molecular pathways in adults living with FTLD. 'Hub' proteins driving co-expression of affected modules warrant further attention as candidate biomarkers and therapeutic targets.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Res Sq Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Res Sq Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos