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@ARTICLE{Fazeli:281734,
      author       = {Fazeli, Badrieh and Botzenhardt, Sara and Bachhuber,
                      Franziska and Klassen, Paula Cynthia and Klose, Veronika and
                      Dorst, Johannes and Wiesenfarth, Maximilian and Uzelac,
                      Zeljko and Jesse, Sarah and Brenner, David and
                      Anderl-Straub, Sarah and Ludolph, Albert and Otto, Markus
                      and Weishaupt, Jochen and Tumani, Hayrettin and Halbgebauer,
                      Steffen},
      title        = {{C}omparative analysis of cerebrospinal fluid neurofilament
                      medium, light and heavy chain in neurodegenerative diseases
                      using an in-house assay for the detection of neurofilament
                      medium chain.},
      journal      = {EBioMedicine},
      volume       = {120},
      issn         = {2352-3964},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier},
      reportid     = {DZNE-2025-01167},
      pages        = {105930},
      year         = {2025},
      abstract     = {Neurofilaments are key axonal proteins, with neurofilament
                      light (NfL) and heavy (NfH) chain recognised as promising
                      biomarkers for neurodegenerative diseases such as
                      amyotrophic lateral sclerosis (ALS). However, neurofilament
                      medium chain (NfM) remained previously underexplored due to
                      a lack of quantitative assays. In this study, we developed a
                      sensitive immunoassay to measure NfM in cerebrospinal fluid
                      (CSF) and analysed its levels in ALS, Alzheimer's disease
                      (AD), frontotemporal dementia (FTD), and Lewy body dementia
                      (LBD). Correlations among neurofilaments and their
                      diagnostic performance were also evaluated.In this study CSF
                      levels of three neurofilament proteins were measured in 305
                      participants, including patients with ALS (n = 91), AD (n =
                      59), FTD (n = 38), LBD (n = 18), non-neurodegenerative
                      controls (CTRL, n = 51), and 48 individuals initially
                      evaluated for ALS but ultimately diagnosed with other
                      conditions (CTRL.DD). NfM levels were quantified using a
                      homemade sandwich ELISA, while NfL and NfH were measured
                      using commercialised Ella cartridges.All three
                      neurofilaments were significantly elevated in ALS compared
                      to CTRL and CTRL.DD groups (p < 0.0001 for both), with NfM
                      and NfL also increased in FTD (p < 0.0001 for both) and AD
                      (NfM, p < 0.0001; NfL, p = 0.0001) compared to CTRL. NfH
                      demonstrated the greatest distinction between ALS and FTD (p
                      < 0.0001). Strong correlations were observed among
                      neurofilament subunits, particularly between NfM and NfL (r
                      = 0.93, $95\%$ CI: 0.91-0.94, p < 0.0001). All
                      neurofilaments effectively distinguished ALS from CTRL and
                      CTRL.DD, with AUC values ranging from 0.92 to 0.99. NfM and
                      NfL showed high accuracy in differentiating AD (NfM, AUC:
                      0.91; NfL, AUC: 0.89) and FTD (NfM, AUC: 0.91; NfL, AUC:
                      0.92) from CTRL, while NfH best separated ALS from FTD (AUC:
                      0.96).This study provides a quantitative comparison of NfM
                      with NfL and NfH in a neurodegenerative cohort, highlighting
                      its potential diagnostic value. Further research with larger
                      cohorts, longitudinal studies, and investigations into
                      neurofilament distribution in different compartments is
                      needed to clarify the distinct roles of NfM, NfL, and NfH in
                      the diagnosis and treatment of neurological diseases.The
                      present study was supported by the Else Kroener-Fresenius
                      Foundation (2024-EKEA.126) and Chemische Fabrik Karl Bucher
                      GmbH.},
      keywords     = {Humans / Neurofilament Proteins: cerebrospinal fluid / Male
                      / Female / Biomarkers: cerebrospinal fluid /
                      Neurodegenerative Diseases: cerebrospinal fluid /
                      Neurodegenerative Diseases: diagnosis / Aged / Middle Aged /
                      Amyotrophic Lateral Sclerosis: cerebrospinal fluid /
                      Amyotrophic Lateral Sclerosis: diagnosis / ROC Curve / Aged,
                      80 and over / Frontotemporal Dementia: cerebrospinal fluid /
                      Frontotemporal Dementia: diagnosis / Alzheimer's diseases
                      (Other) / Amyotrophic lateral sclerosis (Other) / ELISA
                      (Other) / Fluid biomarkers (Other) / Neurofilament medium
                      chain (Other) / Neurofilament Proteins (NLM Chemicals) /
                      Biomarkers (NLM Chemicals) / neurofilament protein L (NLM
                      Chemicals) / neurofilament protein M (NLM Chemicals) /
                      neurofilament protein H (NLM Chemicals)},
      cin          = {Clinical Study Center (Ulm) / AG Zhan},
      ddc          = {610},
      cid          = {I:(DE-2719)5000077 / I:(DE-2719)1910005},
      pnm          = {353 - Clinical and Health Care Research (POF4-353) / 354 -
                      Disease Prevention and Healthy Aging (POF4-354)},
      pid          = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-354},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40974909},
      pmc          = {pmc:PMC12481134},
      doi          = {10.1016/j.ebiom.2025.105930},
      url          = {https://pub.dzne.de/record/281734},
}