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@ARTICLE{Verde:282295,
      author       = {Verde, Federico and Vávra, Jakub and Dorst, J. and Elmas,
                      Zeynep and Wiesenfarth, Maximilian and De Gobbi, Anna and
                      Ratti, Antonia and Poletti, Barbara and Tumani, Hayrettin
                      and Weishaupt, Jochen and Silani, Vincenzo and Ticozzi,
                      Nicola and Otto, Markus and Ludolph, Albert C and Oeckl,
                      Patrick},
      title        = {{CSF} levels of the somatodendritic protein {MAP}2 are
                      increased in {ALS} and predict shorter survival.},
      journal      = {Journal of neurology, neurosurgery, and psychiatry},
      volume       = {96},
      number       = {12},
      issn         = {0022-3050},
      address      = {London},
      publisher    = {BMJ Publishing Group},
      reportid     = {DZNE-2025-01265},
      pages        = {1132 - 1143},
      year         = {2025},
      abstract     = {Previous proteomic work has identified the somatodendritic
                      protein MAP2 as a new candidate cerebrospinal fluid (CSF)
                      biomarker for amyotrophic lateral sclerosis (ALS).We
                      measured CSF levels of MAP2 and neurofilament light chain
                      (NFL) in a retrospective cohort of 251 patients with ALS and
                      108 neurological controls (NCs).Patients with ALS had a
                      higher median CSF MAP2 level compared with NCs, leading to
                      an area under the curve (AUC) of 0.7080 (p<0.0001). They
                      also had a higher median CSF NFL level (p<0.0001), resulting
                      in an excellent diagnostic performance (AUC=0.9641;
                      p<0.0001). Among patients with ALS, CSF MAP2 correlated with
                      disease progression rate (DPR) (r=0.3099; p<0.0001) and was
                      negatively associated with survival (HR=3.174). CSF NFL also
                      correlated with DPR (r=0.4936; p<0.0001) and was negatively
                      associated with survival (HR=2.759). The association of MAP2
                      with DPR was independent from NFL (p=0.0037). Stratifying
                      patients based on median levels of both biomarkers resulted
                      in significant differences in median survival times (low
                      NFL/low MAP2, 66 months; high NFL/low MAP2 and vice versa,
                      35 months; high NFL/high MAP2, 26 months; p<0.0001). MAP2
                      was also associated with genetic status in patients with
                      ALS, as patients with no mutations in C9ORF72 or in SOD1, as
                      well as C9ORF72-positive ones, had higher median levels
                      compared with NCs (p<0.0001), while patients with SOD1
                      mutations did not significantly differ from NCs
                      (p>0.9999).Our study shows that the somatodendritic protein
                      MAP2 is a promising candidate CSF biomarker for ALS.},
      keywords     = {Humans / Amyotrophic Lateral Sclerosis: cerebrospinal fluid
                      / Amyotrophic Lateral Sclerosis: mortality / Amyotrophic
                      Lateral Sclerosis: genetics / Male / Female / Middle Aged /
                      Biomarkers: cerebrospinal fluid / Neurofilament Proteins:
                      cerebrospinal fluid / Aged / Retrospective Studies /
                      Microtubule-Associated Proteins: cerebrospinal fluid /
                      Disease Progression / C9orf72 Protein: genetics / Adult /
                      Superoxide Dismutase-1: genetics / ALS (Other) / CSF (Other)
                      / MOTOR NEURON DISEASE (Other) / Biomarkers (NLM Chemicals)
                      / Neurofilament Proteins (NLM Chemicals) / neurofilament
                      protein L (NLM Chemicals) / Microtubule-Associated Proteins
                      (NLM Chemicals) / MAP2 protein, human (NLM Chemicals) /
                      C9orf72 Protein (NLM Chemicals) / Superoxide Dismutase-1
                      (NLM Chemicals) / C9orf72 protein, human (NLM Chemicals)},
      cin          = {AG Öckl / Clinical Study Center (Ulm)},
      ddc          = {610},
      cid          = {I:(DE-2719)5000073 / I:(DE-2719)5000077},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40537251},
      doi          = {10.1136/jnnp-2025-336208},
      url          = {https://pub.dzne.de/record/282295},
}