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@ARTICLE{Mravinacov:274024,
      author       = {Mravinacová, Sára and Bergström, Sofia and Olofsson,
                      Jennie and de San José, Nerea Gómez and Anderl-Straub,
                      Sarah and Diehl-Schmid, Janine and Fassbender, Klaus and
                      Fliessbach, Klaus and Jahn, Holger and Kornhuber, Johannes
                      and Landwehrmeyer, Georg Bernhard and Lauer, Martin and
                      Levin, Johannes and Ludolph, Albert C and Prudlo, Johannes
                      and Schneider, Anja and Schroeter, Matthias L and Wiltfang,
                      Jens and Steinacker, Petra and Otto, Markus and Nilsson,
                      Peter and Månberg, Anna},
      collaboration = {Consortium, FTLD},
      title        = {{A}ddressing inter individual variability in {CSF} levels
                      of brain derived proteins across neurodegenerative
                      diseases.},
      journal      = {Scientific reports},
      volume       = {15},
      number       = {1},
      issn         = {2045-2322},
      address      = {[London]},
      publisher    = {Macmillan Publishers Limited, part of Springer Nature},
      reportid     = {DZNE-2025-00005},
      pages        = {668},
      year         = {2025},
      abstract     = {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.},
      keywords     = {Humans / Neurodegenerative Diseases: cerebrospinal fluid /
                      Neurodegenerative Diseases: diagnosis / Biomarkers:
                      cerebrospinal fluid / Male / Female / Aged / Middle Aged /
                      Brain: metabolism / Brain: pathology / Alzheimer Disease:
                      cerebrospinal fluid / Alzheimer Disease: diagnosis /
                      Cerebrospinal Fluid Proteins: analysis / Amyotrophic Lateral
                      Sclerosis: cerebrospinal fluid / Amyotrophic Lateral
                      Sclerosis: diagnosis / Affinity proteomics (Other) /
                      Biomarker (Other) / Cerebrospinal fluid (Other) /
                      Inter-individual variability (Other) / Multi-disease (Other)
                      / Neurodegeneration (Other) / Biomarkers (NLM Chemicals) /
                      Cerebrospinal Fluid Proteins (NLM Chemicals)},
      cin          = {Patient Studies (Bonn) / AG Wiltfang / Clinical Research
                      (Munich) / Clinical Study Center (Ulm) / AG Teipel / AG
                      Schneider},
      ddc          = {600},
      cid          = {I:(DE-2719)1011101 / I:(DE-2719)1410006 /
                      I:(DE-2719)1111015 / I:(DE-2719)5000077 / I:(DE-2719)1510100
                      / I:(DE-2719)1011305},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39753643},
      pmc          = {pmc:PMC11698900},
      doi          = {10.1038/s41598-024-83281-y},
      url          = {https://pub.dzne.de/record/274024},
}