{
  "abstract": "Background Previous proteomic work has identified the somatodendritic protein MAP2 as a new candidate cerebrospinal fluid (CSF) biomarker for amyotrophic lateral sclerosis (ALS).Methods 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).Results 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).Conclusions Our study shows that the somatodendritic protein MAP2 is a promising candidate CSF biomarker for ALS.",
  "authors": [
    {
      "affiliations": [
        "Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy",
        "Department of Pathophysiology and Transplantation, „Dino Ferrari” Center, Università degli Studi di Milano, Milan, Italy"
      ],
      "name": "Federico Verde"
    },
    {
      "affiliations": [
        "German Center for Neurodegenerative Diseases (DZNE) Ulm, Ulm, Germany"
      ],
      "name": "Jakub Vávra"
    },
    {
      "affiliations": [
        "German Center for Neurodegenerative Diseases (DZNE) Ulm, Ulm, Germany",
        "Department of Neurology, Ulm University Hospital, Ulm, Germany"
      ],
      "name": "J Dorst"
    },
    {
      "affiliations": [
        "Department of Neurology, Ulm University Hospital, Ulm, Germany"
      ],
      "name": "Zeynep Elmas"
    },
    {
      "affiliations": [
        "Department of Neurology, Ulm University Hospital, Ulm, Germany"
      ],
      "name": "Maximilian Wiesenfarth"
    },
    {
      "affiliations": [
        "Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy"
      ],
      "name": "Anna De Gobbi"
    },
    {
      "affiliations": [
        "Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy",
        "Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Milan, Italy"
      ],
      "name": "Antonia Ratti"
    },
    {
      "affiliations": [
        "Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy",
        "Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Milan, Italy"
      ],
      "name": "Barbara Poletti"
    },
    {
      "affiliations": [
        "Department of Neurology, Ulm University Hospital, Ulm, Germany"
      ],
      "name": "Hayrettin Tumani"
    },
    {
      "affiliations": [
        "Department of Neurology, Ulm University Hospital, Ulm, Germany"
      ],
      "name": "Jochen Weishaupt"
    },
    {
      "affiliations": [
        "Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy",
        "Department of Pathophysiology and Transplantation, „Dino Ferrari” Center, Università degli Studi di Milano, Milan, Italy"
      ],
      "name": "Vincenzo Silani"
    },
    {
      "affiliations": [
        "Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy",
        "Department of Pathophysiology and Transplantation, „Dino Ferrari” Center, Università degli Studi di Milano, Milan, Italy"
      ],
      "name": "Nicola Ticozzi"
    },
    {
      "affiliations": [
        "Department of Neurology, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany"
      ],
      "name": "Markus Otto"
    },
    {
      "affiliations": [
        "German Center for Neurodegenerative Diseases (DZNE) Ulm, Ulm, Germany",
        "Department of Neurology, Ulm University Hospital, Ulm, Germany"
      ],
      "name": "Albert C Ludolph"
    },
    {
      "affiliations": [
        "German Center for Neurodegenerative Diseases (DZNE) Ulm, Ulm, Germany",
        "Department of Neurology, Ulm University Hospital, Ulm, Germany"
      ],
      "name": "Patrick Oeckl"
    }
  ],
  "title": "CSF levels of the somatodendritic protein MAP2 are increased in ALS and predict shorter survival",
  "uid": "f04ff809-d70c-5103-9d57-f48b95599778"
}