Proteome profiling in cerebrospinal fluid reveals novel biomarkers of Alzheimer's disease.
Alzheimer's disease
cerebrospinal fluid
mass spectrometry
neurodegeneration
proteomics
Journal
Molecular systems biology
ISSN: 1744-4292
Titre abrégé: Mol Syst Biol
Pays: England
ID NLM: 101235389
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
14
11
2019
revised:
29
04
2020
accepted:
30
04
2020
entrez:
3
6
2020
pubmed:
3
6
2020
medline:
9
7
2021
Statut:
ppublish
Résumé
Neurodegenerative diseases are a growing burden, and there is an urgent need for better biomarkers for diagnosis, prognosis, and treatment efficacy. Structural and functional brain alterations are reflected in the protein composition of cerebrospinal fluid (CSF). Alzheimer's disease (AD) patients have higher CSF levels of tau, but we lack knowledge of systems-wide changes of CSF protein levels that accompany AD. Here, we present a highly reproducible mass spectrometry (MS)-based proteomics workflow for the in-depth analysis of CSF from minimal sample amounts. From three independent studies (197 individuals), we characterize differences in proteins by AD status (> 1,000 proteins, CV < 20%). Proteins with previous links to neurodegeneration such as tau, SOD1, and PARK7 differed most strongly by AD status, providing strong positive controls for our approach. CSF proteome changes in Alzheimer's disease prove to be widespread and often correlated with tau concentrations. Our unbiased screen also reveals a consistent glycolytic signature across our cohorts and a recent study. Machine learning suggests clinical utility of this proteomic signature.
Identifiants
pubmed: 32485097
doi: 10.15252/msb.20199356
pmc: PMC7266499
doi:
Substances chimiques
Biomarkers
0
Proteome
0
tau Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e9356Informations de copyright
© 2020 The Authors. Published under the terms of the CC BY 4.0 license.
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