Home > Publications Database > Addressing inter individual variability in CSF levels of brain derived proteins across neurodegenerative diseases. > print

001     274024
005     20250119000228.0
024 7 _ |a 10.1038/s41598-024-83281-y
|2 doi
024 7 _ |a pmid:39753643
|2 pmid
024 7 _ |a pmc:PMC11698900
|2 pmc
024 7 _ |a altmetric:172919227
|2 altmetric
037 _ _ |a DZNE-2025-00005
041 _ _ |a English
082 _ _ |a 600
100 1 _ |a Mravinacová, Sára
|b 0
245 _ _ |a Addressing inter individual variability in CSF levels of brain derived proteins across neurodegenerative diseases.
260 _ _ |a [London]
|c 2025
|b Macmillan Publishers Limited, part of Springer Nature
336 7 _ |a article
|2 DRIVER
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|b journal
|m journal
|0 PUB:(DE-HGF)16
|s 1736939235_31493
|2 PUB:(DE-HGF)
336 7 _ |a ARTICLE
|2 BibTeX
336 7 _ |a JOURNAL_ARTICLE
|2 ORCID
336 7 _ |a Journal Article
|0 0
|2 EndNote
520 _ _ |a Accurate diagnosis and monitoring of neurodegenerative diseases require reliable biomarkers. Cerebrospinal fluid (CSF) proteins are promising candidates for reflecting brain pathology; however, their diagnostic utility may be compromised by natural variability between individuals, weakening their association with disease. Here, we measured the levels of 69 pre-selected proteins in cerebrospinal fluid using antibody-based suspension bead array technology in a multi-disease cohort of 499 individuals with neurodegenerative disorders including Alzheimer's disease (AD), behavioral variant frontotemporal dementia, primary progressive aphasias, amyotrophic lateral sclerosis (ALS), corticobasal syndrome, primary supranuclear palsy, along with healthy controls. We identify significant inter-individual variability in overall CSF levels of brain-derived proteins, which could not be attributed to specific disease associations. Using linear modelling, we show that adjusting for median CSF levels of brain-derived proteins increases the diagnostic accuracy of proteins previously identified as altered in CSF in the context of neurodegenerative disorders. We further demonstrate a simplified approach for the adjustment using pairs of correlated proteins with opposite alteration in the diseases. With this approach, the proteins adjust for each other and further increase the biomarker performance through additive effect. When comparing the diseases, two proteins-neurofilament medium and myelin basic protein-showed increased levels in ALS compared to other diseases, and neurogranin showed a specific increase in AD. Several other proteins showed similar trends across the studied diseases, indicating that these proteins likely reflect shared processes related to neurodegeneration. Overall, our findings suggest that accounting for inter-individual variability is crucial in future studies to improve the identification and performance of relevant biomarkers. Importantly, we highlight the need for multi-disease studies to identify disease-specific biomarkers.
536 _ _ |a 353 - Clinical and Health Care Research (POF4-353)
|0 G:(DE-HGF)POF4-353
|c POF4-353
|f POF IV
|x 0
588 _ _ |a Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
650 _ 7 |a Affinity proteomics
|2 Other
650 _ 7 |a Biomarker
|2 Other
650 _ 7 |a Cerebrospinal fluid
|2 Other
650 _ 7 |a Inter-individual variability
|2 Other
650 _ 7 |a Multi-disease
|2 Other
650 _ 7 |a Neurodegeneration
|2 Other
650 _ 7 |a Biomarkers
|2 NLM Chemicals
650 _ 7 |a Cerebrospinal Fluid Proteins
|2 NLM Chemicals
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Neurodegenerative Diseases: cerebrospinal fluid
|2 MeSH
650 _ 2 |a Neurodegenerative Diseases: diagnosis
|2 MeSH
650 _ 2 |a Biomarkers: cerebrospinal fluid
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Aged
|2 MeSH
650 _ 2 |a Middle Aged
|2 MeSH
650 _ 2 |a Brain: metabolism
|2 MeSH
650 _ 2 |a Brain: pathology
|2 MeSH
650 _ 2 |a Alzheimer Disease: cerebrospinal fluid
|2 MeSH
650 _ 2 |a Alzheimer Disease: diagnosis
|2 MeSH
650 _ 2 |a Cerebrospinal Fluid Proteins: analysis
|2 MeSH
650 _ 2 |a Amyotrophic Lateral Sclerosis: cerebrospinal fluid
|2 MeSH
650 _ 2 |a Amyotrophic Lateral Sclerosis: diagnosis
|2 MeSH
700 1 _ |a Bergström, Sofia
|b 1
700 1 _ |a Olofsson, Jennie
|b 2
700 1 _ |a de San José, Nerea Gómez
|b 3
700 1 _ |a Anderl-Straub, Sarah
|b 4
700 1 _ |a Diehl-Schmid, Janine
|b 5
700 1 _ |a Fassbender, Klaus
|b 6
700 1 _ |a Fliessbach, Klaus
|0 P:(DE-2719)2811326
|b 7
|u dzne
700 1 _ |a Jahn, Holger
|b 8
700 1 _ |a Kornhuber, Johannes
|b 9
700 1 _ |a Landwehrmeyer, Georg Bernhard
|0 P:(DE-2719)9003425
|b 10
|u dzne
700 1 _ |a Lauer, Martin
|b 11
700 1 _ |a Levin, Johannes
|0 P:(DE-2719)2811659
|b 12
|u dzne
700 1 _ |a Ludolph, Albert C
|0 P:(DE-2719)2812633
|b 13
|u dzne
700 1 _ |a Prudlo, Johannes
|0 P:(DE-2719)2380559
|b 14
|u dzne
700 1 _ |a Schneider, Anja
|0 P:(DE-2719)2812035
|b 15
|u dzne
700 1 _ |a Schroeter, Matthias L
|b 16
700 1 _ |a Wiltfang, Jens
|0 P:(DE-2719)2811317
|b 17
|u dzne
700 1 _ |a Steinacker, Petra
|b 18
700 1 _ |a Consortium, FTLD
|b 19
|e Collaboration Author
700 1 _ |a Otto, Markus
|b 20
700 1 _ |a Nilsson, Peter
|b 21
700 1 _ |a Månberg, Anna
|b 22
773 _ _ |a 10.1038/s41598-024-83281-y
|g Vol. 15, no. 1, p. 668
|0 PERI:(DE-600)2615211-3
|n 1
|p 668
|t Scientific reports
|v 15
|y 2025
|x 2045-2322
856 4 _ |u https://pub.dzne.de/record/274024/files/DZNE-2025-00005%20SUP.pdf
856 4 _ |y OpenAccess
|u https://pub.dzne.de/record/274024/files/DZNE-2025-00005.pdf
856 4 _ |x pdfa
|u https://pub.dzne.de/record/274024/files/DZNE-2025-00005%20SUP.pdf?subformat=pdfa
856 4 _ |y OpenAccess
|x pdfa
|u https://pub.dzne.de/record/274024/files/DZNE-2025-00005.pdf?subformat=pdfa
909 C O |o oai:pub.dzne.de:274024
|p openaire
|p open_access
|p VDB
|p driver
|p dnbdelivery
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 7
|6 P:(DE-2719)2811326
910 1 _ |a External Institute
|0 I:(DE-HGF)0
|k Extern
|b 10
|6 P:(DE-2719)9003425
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 12
|6 P:(DE-2719)2811659
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 13
|6 P:(DE-2719)2812633
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 14
|6 P:(DE-2719)2380559
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 15
|6 P:(DE-2719)2812035
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 17
|6 P:(DE-2719)2811317
913 1 _ |a DE-HGF
|b Gesundheit
|l Neurodegenerative Diseases
|1 G:(DE-HGF)POF4-350
|0 G:(DE-HGF)POF4-353
|3 G:(DE-HGF)POF4
|2 G:(DE-HGF)POF4-300
|4 G:(DE-HGF)POF
|v Clinical and Health Care Research
|x 0
914 1 _ |y 2025
915 _ _ |a Creative Commons Attribution CC BY 4.0
|0 LIC:(DE-HGF)CCBY4
|2 HGFVOC
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0200
|2 StatID
|b SCOPUS
|d 2023-08-24
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0160
|2 StatID
|b Essential Science Indicators
|d 2023-08-24
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1050
|2 StatID
|b BIOSIS Previews
|d 2023-08-24
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1190
|2 StatID
|b Biological Abstracts
|d 2023-08-24
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0600
|2 StatID
|b Ebsco Academic Search
|d 2023-08-24
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1040
|2 StatID
|b Zoological Record
|d 2023-08-24
915 _ _ |a JCR
|0 StatID:(DE-HGF)0100
|2 StatID
|b SCI REP-UK : 2022
|d 2023-08-24
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0501
|2 StatID
|b DOAJ Seal
|d 2023-04-12T15:11:06Z
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0500
|2 StatID
|b DOAJ
|d 2023-04-12T15:11:06Z
915 _ _ |a WoS
|0 StatID:(DE-HGF)0113
|2 StatID
|b Science Citation Index Expanded
|d 2023-08-24
915 _ _ |a Fees
|0 StatID:(DE-HGF)0700
|2 StatID
|d 2023-08-24
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0150
|2 StatID
|b Web of Science Core Collection
|d 2023-08-24
915 _ _ |a IF < 5
|0 StatID:(DE-HGF)9900
|2 StatID
|d 2023-08-24
915 _ _ |a OpenAccess
|0 StatID:(DE-HGF)0510
|2 StatID
915 _ _ |a Peer Review
|0 StatID:(DE-HGF)0030
|2 StatID
|b ASC
|d 2023-08-24
915 _ _ |a Article Processing Charges
|0 StatID:(DE-HGF)0561
|2 StatID
|d 2023-08-24
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1150
|2 StatID
|b Current Contents - Physical, Chemical and Earth Sciences
|d 2023-08-24
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0300
|2 StatID
|b Medline
|d 2023-08-24
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0320
|2 StatID
|b PubMed Central
|d 2023-08-24
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0199
|2 StatID
|b Clarivate Analytics Master Journal List
|d 2023-08-24
920 1 _ |0 I:(DE-2719)1011101
|k Patient Studies (Bonn)
|l Patient Studies (Bonn)
|x 0
920 1 _ |0 I:(DE-2719)1410006
|k AG Wiltfang
|l Molecular biomarkers for predictive diagnostics of neurodegenerative diseases
|x 1
920 1 _ |0 I:(DE-2719)1111015
|k Clinical Research (Munich)
|l Clinical Research (Munich)
|x 2
920 1 _ |0 I:(DE-2719)5000077
|k Clinical Study Center (Ulm)
|l Clinical Study Center (Ulm)
|x 3
920 1 _ |0 I:(DE-2719)1510100
|k AG Teipel
|l Clinical Dementia Research (Rostock /Greifswald)
|x 4
920 1 _ |0 I:(DE-2719)1011305
|k AG Schneider
|l Translational Dementia Research (Bonn)
|x 5
980 _ _ |a journal
980 _ _ |a VDB
980 _ _ |a UNRESTRICTED
980 _ _ |a I:(DE-2719)1011101
980 _ _ |a I:(DE-2719)1410006
980 _ _ |a I:(DE-2719)1111015
980 _ _ |a I:(DE-2719)5000077
980 _ _ |a I:(DE-2719)1510100
980 _ _ |a I:(DE-2719)1011305
980 1 _ |a FullTexts

LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21