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@ARTICLE{Halbgebauer:282577,
      author       = {Halbgebauer, Steffen and Fazeli, Badrieh and Klose,
                      Veronika and Nagel, Gabriele and Rosenbohm, Angela and
                      Rothenbacher, Dietrich and Bachhuber, Franziska and Jesse,
                      Sarah and Otto, Markus and Landwehrmeyer, Georg Bernhard and
                      Abdelhak, Ahmed and Petzold, Axel and Ludolph, Albert C and
                      Tumani, Hayrettin},
      title        = {{A}ge-{S}pecific {C}ontrol and {A}lzheimer {D}isease
                      {R}eference {C}urves and z-{S}cores for {G}lial {F}ibrillary
                      {A}cidic {P}rotein in {B}lood.},
      journal      = {Clinical chemistry},
      volume       = {71},
      number       = {12},
      issn         = {0009-9147},
      address      = {Washington, DC},
      publisher    = {American Association for Clinical Chemistry},
      reportid     = {DZNE-2025-01337},
      pages        = {1234 - 1242},
      year         = {2025},
      abstract     = {Serum glial fibrillary acidic protein (GFAP) is a biomarker
                      for astrocytic injury and astrogliosis. Concentrations are
                      elevated in numerous neurological disorders, including a
                      pronounced increase in Alzheimer disease (AD). However, GFAP
                      levels in the serum also increase with age. Consequently,
                      the integration of GFAP levels into clinical routine and
                      their interpretation demands age-adjusted reference
                      values.Serum from 1273 subjects (952 noninflammatory and
                      nonneurodegenerative neurological controls and 321 subjects
                      with AD) was analyzed for GFAP using the microfluidic Ella
                      system. Age-dependent serum GFAP reference values were
                      estimated by additive quantile regression analysis and
                      visualized with percentiles and z-scores.AD exhibited
                      elevated serum GFAP levels in comparison to control patients
                      (P < 0.0001). This remained the case when the newly
                      generated age-corrected z-scores were applied (P < 0.0001).
                      In the control cohort, a nonlinear elevation of serum GFAP
                      with increasing age was observed (Spearman correlation
                      coefficient 0.62, $95\%$ CI 0.58-0.66, P < 0.0001). In
                      contrast, the AD cohort exhibited a more linear increase
                      (0.16, $95\%$ CI 0.05-0.26, P = 0.004). Age-dependent
                      cut-offs for serum GFAP were determined for different AD age
                      groups. The calculated areas under the curve (AUCs; 0.97)
                      demonstrated excellent diagnostic test performance in the
                      early-onset age group. This effect was less marked in the
                      elderly subjects (AUC 0.72).Our novel GFAP z-scores enable
                      the integration and interpretation of serum GFAP levels in
                      clinical practice, moving from the group to individual
                      level. They support both intra- and interindividual
                      interpretation of single GFAP levels in neurological
                      diseases with astrocytic pathology, including an accurate
                      discrimination of AD.},
      keywords     = {Humans / Alzheimer Disease: blood / Alzheimer Disease:
                      diagnosis / Glial Fibrillary Acidic Protein: blood / Aged /
                      Male / Female / Middle Aged / Reference Values / Biomarkers:
                      blood / Aged, 80 and over / Age Factors / Adult /
                      Case-Control Studies / Glial Fibrillary Acidic Protein (NLM
                      Chemicals) / Biomarkers (NLM Chemicals) / GFAP protein,
                      human (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:41081630},
      doi          = {10.1093/clinchem/hvaf120},
      url          = {https://pub.dzne.de/record/282577},
}