Proteome profiling in cerebrospinal fluid reveals novel biomarkers of Alzheimer's disease
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 (A...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2020-06-01
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| Series: | Molecular Systems Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/msb.20199356 |
| _version_ | 1797285196436865024 |
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| author | Jakob M Bader Philipp E Geyer Johannes B Müller Maximilian T Strauss Manja Koch Frank Leypoldt Peter Koertvelyessy Daniel Bittner Carola G Schipke Enise I Incesoy Oliver Peters Nikolaus Deigendesch Mikael Simons Majken K Jensen Henrik Zetterberg Matthias Mann |
| author_facet | Jakob M Bader Philipp E Geyer Johannes B Müller Maximilian T Strauss Manja Koch Frank Leypoldt Peter Koertvelyessy Daniel Bittner Carola G Schipke Enise I Incesoy Oliver Peters Nikolaus Deigendesch Mikael Simons Majken K Jensen Henrik Zetterberg Matthias Mann |
| author_sort | Jakob M Bader |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T17:59:47Z |
| format | Article |
| id | doaj.art-80195a6e8c6a486e943130141f08bd7a |
| institution | Directory Open Access Journal |
| issn | 1744-4292 |
| language | English |
| last_indexed | 2024-03-07T17:59:47Z |
| publishDate | 2020-06-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj.art-80195a6e8c6a486e943130141f08bd7a2024-03-02T11:11:30ZengSpringer NatureMolecular Systems Biology1744-42922020-06-01166n/an/a10.15252/msb.20199356Proteome profiling in cerebrospinal fluid reveals novel biomarkers of Alzheimer's diseaseJakob M Bader0Philipp E Geyer1Johannes B Müller2Maximilian T Strauss3Manja Koch4Frank Leypoldt5Peter Koertvelyessy6Daniel Bittner7Carola G Schipke8Enise I Incesoy9Oliver Peters10Nikolaus Deigendesch11Mikael Simons12Majken K Jensen13Henrik Zetterberg14Matthias Mann15Department of Proteomics and Signal Transduction Max Planck Institute of Biochemistry Martinsried GermanyDepartment of Proteomics and Signal Transduction Max Planck Institute of Biochemistry Martinsried GermanyDepartment of Proteomics and Signal Transduction Max Planck Institute of Biochemistry Martinsried GermanyDepartment of Proteomics and Signal Transduction Max Planck Institute of Biochemistry Martinsried GermanyDepartments of Nutrition & Epidemiology Harvard T.H. Chan School of Public Health Boston MA USAInstitute of Clinical Chemistry Faculty of Medicine Kiel University Kiel GermanyDepartment of Neurology Medical Faculty Otto von Guericke University Magdeburg Magdeburg GermanyDepartment of Neurology Medical Faculty Otto von Guericke University Magdeburg Magdeburg GermanyExperimental & Clinical Research Center (ECRC), Charité – Universitätsmedizin Berlin corporate member of Freie Universität Berlin Humboldt‐Universität zu Berlin, & Berlin Institute of Health Berlin GermanyDepartment of Psychiatry corporate member of Freie Universität Berlin, Humboldt‐Universität zu Berlin & Berlin Institute of Health, Charité Universitätsmedizin Berlin Berlin GermanyDepartment of Psychiatry corporate member of Freie Universität Berlin, Humboldt‐Universität zu Berlin & Berlin Institute of Health, Charité Universitätsmedizin Berlin Berlin GermanyInstitute of Medical Genetics and Pathology University Hospital Basel Basel SwitzerlandGerman Center for Neurodegenerative Diseases (DZNE) Munich GermanyDepartments of Nutrition & Epidemiology Harvard T.H. Chan School of Public Health Boston MA USADepartment of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology the Sahlgrenska Academy at the University of Gothenburg Mölndal SwedenDepartment of Proteomics and Signal Transduction Max Planck Institute of Biochemistry Martinsried GermanyAbstract 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.https://doi.org/10.15252/msb.20199356Alzheimer's diseasecerebrospinal fluidmass spectrometryneurodegenerationproteomics |
| spellingShingle | Jakob M Bader Philipp E Geyer Johannes B Müller Maximilian T Strauss Manja Koch Frank Leypoldt Peter Koertvelyessy Daniel Bittner Carola G Schipke Enise I Incesoy Oliver Peters Nikolaus Deigendesch Mikael Simons Majken K Jensen Henrik Zetterberg Matthias Mann Proteome profiling in cerebrospinal fluid reveals novel biomarkers of Alzheimer's disease Molecular Systems Biology Alzheimer's disease cerebrospinal fluid mass spectrometry neurodegeneration proteomics |
| title | Proteome profiling in cerebrospinal fluid reveals novel biomarkers of Alzheimer's disease |
| title_full | Proteome profiling in cerebrospinal fluid reveals novel biomarkers of Alzheimer's disease |
| title_fullStr | Proteome profiling in cerebrospinal fluid reveals novel biomarkers of Alzheimer's disease |
| title_full_unstemmed | Proteome profiling in cerebrospinal fluid reveals novel biomarkers of Alzheimer's disease |
| title_short | Proteome profiling in cerebrospinal fluid reveals novel biomarkers of Alzheimer's disease |
| title_sort | proteome profiling in cerebrospinal fluid reveals novel biomarkers of alzheimer s disease |
| topic | Alzheimer's disease cerebrospinal fluid mass spectrometry neurodegeneration proteomics |
| url | https://doi.org/10.15252/msb.20199356 |
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