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

Bader, J. M., Geyer, P. E., Müller, J. B., Strauss, M. T., Koch, M., Leypoldt, F., et al. (2020). Proteome profiling in cerebrospinal fluid reveals novel biomarkers of Alzheimer's disease. MOLECULAR SYSTEMS BIOLOGY, 16(6): e9356. doi:10.15252/msb.20199356.

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 Creators:
Bader, Jakob M.1, Author              
Geyer, Philipp E.1, Author              
Müller, Johannes B.1, Author              
Strauss, Maximilian T.1, Author              
Koch, Manja2, Author
Leypoldt, Frank2, Author
Koertvelyessy, Peter2, Author
Bittner, Daniel2, Author
Schipke, Carola G.2, Author
Incesoy, Enise I.2, Author
Peters, Oliver2, Author
Deigendesch, Nikolaus2, Author
Simons, Mikael2, Author
Jensen, Majken K.2, Author
Zetterberg, Henrik2, Author
Mann, Matthias1, Author              
Affiliations:
1Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159              
2external, ou_persistent22              

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Free keywords: MENTAL-STATE-EXAMINATION; MASS-SPECTROMETRY; AMYLOID-PET; CSF; PLASMA; DEMENTIA; TAU; QUANTIFICATION; METAANALYSIS; ASSOCIATIONAlzheimer's disease; cerebrospinal fluid; mass spectrometry; neurodegeneration; proteomics;
 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 higherCSFlevels of tau, but we lack knowledge of systems-wide changes ofCSFprotein levels that accompanyAD. Here, we present a highly reproducible mass spectrometry (MS)-based proteomics workflow for the in-depth analysis ofCSFfrom minimal sample amounts. From three independent studies (197 individuals), we characterize differences in proteins byADstatus (> 1,000 proteins,CV < 20%). Proteins with previous links to neurodegeneration such as tau,SOD1, andPARK7 differed most strongly byADstatus, providing strong positive controls for our approach.CSFproteome 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.

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Language(s): eng - English
 Dates: 2020
 Publication Status: Published online
 Pages: 17
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000545998800010
DOI: 10.15252/msb.20199356
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Title: MOLECULAR SYSTEMS BIOLOGY
Source Genre: Journal
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Publ. Info: 111 RIVER ST, HOBOKEN 07030-5774, NJ USA : WILEY
Pages: - Volume / Issue: 16 (6) Sequence Number: e9356 Start / End Page: - Identifier: ISSN: 1744-4292