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Proteome profiling in cerebrospinal fluid reveals novel biomarkers of Alzheimer's disease

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Item Type:Article
Title:Proteome profiling in cerebrospinal fluid reveals novel biomarkers of Alzheimer's disease
Creators Name:Bader, J.M. and Geyer, P.E. and Müller, J.B. and Strauss, M.T. and Koch, M. and Leypoldt, F. and Koertvelyessy, P. and Bittner, D. and Schipke, C.G. and Incesoy, E.I. and Peters, O. and Deigendesch, N. and Simons, M. and Jensen, M.K. and Zetterberg, H. and Mann, M.
Abstract: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.
Keywords:Alzheimer's Disease, Cerebrospinal Fluid, Mass Spectrometry, Neurodegeneration, Proteomics
Source:Molecular Systems Biology
ISSN:1744-4292
Publisher:EMBO Press
Volume:16
Number:6
Page Range:e9356
Date:1 June 2020
Official Publication:https://doi.org/10.15252/msb.20199356
PubMed:View item in PubMed

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