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@ARTICLE{Halbgebauer:280116,
      author       = {Halbgebauer, Steffen and Klose, Veronika and Fazeli,
                      Badrieh and Klassen, Paula Cynthia and Alexudis,
                      Christoforos and Nagel, Gabriele and Rosenbohm, Angela and
                      Rothenbacher, Dietrich and Gomez de San Jose, Nerea and
                      Witzel, Simon and Elmas, Zeynep and Wiesenfarth, Maximilian
                      and Schuster, Joachim and Dorst, Johannes and Huss, Andre
                      and Bachhuber, Franziska and Otto, Markus and Landwehrmeyer,
                      Georg Bernhard and Ludolph, Albert C and Tumani, Hayrettin},
      title        = {{N}eurofilament light chain reference values in serum and
                      cerebrospinal fluid: a bi-compartmental analysis in
                      neurological diseases.},
      journal      = {Journal of neurology},
      volume       = {272},
      number       = {8},
      issn         = {0367-004X},
      address      = {[Darmstadt]},
      publisher    = {Steinkopff},
      reportid     = {DZNE-2025-00899},
      pages        = {535},
      year         = {2025},
      abstract     = {Concentrations of neurofilament light chain (NfL), a
                      neuroaxonal damage marker, increase with age. Therefore,
                      age-dependent reference values are important in clinical
                      practice. However, so far these have only been established
                      with a bead-based system and age-dependent z-scores for CSF
                      are missing. In addition, we here propose how the combined
                      analysis of CSF and serum NfL could help in the
                      discrimination between central (CNS) and peripheral nervous
                      system (PNS) axonal degeneration.For the calculation of age
                      reference values, serum and CSF NfL concentrations from
                      1,514 control subjects, measured using the microfluidic Ella
                      system, were applied.Age-dependent NfL levels were
                      calculated with additive quantile regression and presented
                      with percentiles and z-scores. We observed a non-linear
                      increase of NfL in serum and CSF. The spearman r of the
                      association with age was 0.81 $(95\%$ CI 0.78-0.83), p <
                      0.0001 and 0.82 $(95\%$ CI 0.79-0.85), p < 0.0001 for serum
                      and CSF NfL, respectively. Serum and CSF NfL levels were
                      also associated with each other (r = 0.68 $(95\%CI$
                      0.62-0.73), p < 0.0001). Furthermore, we used this
                      association to establish a bi-compartmental CSF and serum
                      NfL model allowing to differentiate between peripheral or
                      central origin of neurodegeneration.The age reference curves
                      corroborate findings of an exponential elevation of NfL in
                      serum and CSF with increasing age. As NfL values from
                      different platforms are not interchangeable, this is of
                      additional high relevance. Moreover, the association between
                      CSF and serum NfL values could be applied for clinical use
                      regarding overlapping symptoms of CNS and PNS-based
                      neurological diseases.},
      keywords     = {Humans / Neurofilament Proteins: blood / Neurofilament
                      Proteins: cerebrospinal fluid / Male / Female / Middle Aged
                      / Adult / Aged / Reference Values / Young Adult / Nervous
                      System Diseases: blood / Nervous System Diseases:
                      cerebrospinal fluid / Nervous System Diseases: diagnosis /
                      Adolescent / Aged, 80 and over / Child / Biomarkers: blood /
                      Biomarkers: cerebrospinal fluid / Child, Preschool / Aging:
                      blood / Aging: cerebrospinal fluid / Age reference values
                      (Other) / Bi-compartment model (Other) / CSF (Other) /
                      Neurofilament (Other) / NfL (Other) / Serum (Other) /
                      Z-score (Other) / Neurofilament Proteins (NLM Chemicals) /
                      neurofilament protein L (NLM Chemicals) / Biomarkers (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:40711597},
      doi          = {10.1007/s00415-025-13271-1},
      url          = {https://pub.dzne.de/record/280116},
}