MassIVE MSV000088649

Imported Reanalysis Dataset Public PXD016278

Proteome Profiling in Cerebrospinal Fluid Reveals Novel Biomarkers of Alzheimer’s Disease

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Description

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 (>200 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 and a recent report (bioRxiv.org doi.org/10.1101/806752). Successful reclassification of individual patients and a machine learning model suggests clinical utility of our proteomic signature. [doi:10.25345/C5GP14] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Alzheimer’s disease/ cerebrospinal fluid/ mass spectrometry/ neurodegeneration/ proteomics

Contact

Principal Investigators:
(in alphabetical order) 		Matthias Mann, Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany NNF Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark, N/A
Submitting User: ccms

Publications

Bader JM, Geyer PE, Müller JB, Strauss MT, Koch M, Leypoldt F, Koertvelyessy P, Bittner D, Schipke CG, Incesoy EI, Peters O, Deigendesch N, Simons M, Jensen MK, Zetterberg H, Mann M.
Proteome profiling in cerebrospinal fluid reveals novel biomarkers of Alzheimer's disease.
Mol Syst Biol. 2020 Jun;16(6):e9356.

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Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

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Number of distinct proteins found to be differentially abundant in at least one comparison across all analyses (original submission and reanalyses) associated with this dataset.

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Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

"N/A" means no results of this type were submitted.
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