title: TDP-43 pathology and cognition in ALS: A prospective clinicopathologic correlation study.
abstract: OBJECTIVE
  Although a systematic spread of pathologic TDP-43 expression throughout the CNS in amyotrophic lateral sclerosis (ALS) has been proposed, the relationship between cognition and the extent and neuroanatomic distribution of TDP-43 pathology has not received considerable attention.
  
  
  METHODS
  We investigated the association between cognitive functioning and the extent of TDP-43 pathology in postmortem CNS tissue from 18 patients with ALS stratified into 3 groups based on detailed prospective neuropsychological testing (cognitively not impaired, n = 6; cognitively impaired, n = 6; ALS- frontotemporal dementia [FTD], n = 6) and analyzed these cases for clinicopathologic correlations.
  
  
  RESULTS
  Our findings demonstrate a close relationship between cognition and the extent of TDP-43 pathology in non-primary motor areas with a striking difference between ALS-FTD and the 2 other cognitive groups. The specificity of our results was underscored by 2 key findings: first, the absence of an Alzheimer pathology effect, a common confounder in older patients; second, the lack of correlations between the primary motor regions with the highest TDP-43 intensity and cognitive status.
  
  
  CONCLUSIONS
  Our data suggest a distinct dynamic of TDP-43 progression and distribution in ALS-FTD in contrast to ALS without FTD.
authors.affiliation: From the Departments of Neurology (J.P.) and Psychosomatic Medicine (E.K., S.T.) and Institute of Forensic Medicine (A.B.), Rostock University Medical Center; German Center for Neurodegenerative Diseases (DZNE) (J.P., S.T.), Rostock; Institute of Medical Biostatistics, Epidemiology and Informatics (J.K.), University Medical Center, Johannes Gutenberg University Mainz, Germany; Quantitative Neuroimaging Group (C.S.), Academic Unit of Neurology, Biomedical Sciences Institute, Trinity College Dublin, Ireland; Department of Neuropathology (M.N.), University Hospital of Tübingen; and German Center for Neurodegenerative Diseases (DZNE) (M.N.), Tübingen, Germany. johannes.prudlo@med.uni-rostock.de.
authors.forename: Johannes
authors.initials: J
authors.lastname: Prudlo
authors.affiliation: From the Departments of Neurology (J.P.) and Psychosomatic Medicine (E.K., S.T.) and Institute of Forensic Medicine (A.B.), Rostock University Medical Center; German Center for Neurodegenerative Diseases (DZNE) (J.P., S.T.), Rostock; Institute of Medical Biostatistics, Epidemiology and Informatics (J.K.), University Medical Center, Johannes Gutenberg University Mainz, Germany; Quantitative Neuroimaging Group (C.S.), Academic Unit of Neurology, Biomedical Sciences Institute, Trinity College Dublin, Ireland; Department of Neuropathology (M.N.), University Hospital of Tübingen; and German Center for Neurodegenerative Diseases (DZNE) (M.N.), Tübingen, Germany.
authors.forename: Jochem
authors.initials: J
authors.lastname: König
authors.affiliation: From the Departments of Neurology (J.P.) and Psychosomatic Medicine (E.K., S.T.) and Institute of Forensic Medicine (A.B.), Rostock University Medical Center; German Center for Neurodegenerative Diseases (DZNE) (J.P., S.T.), Rostock; Institute of Medical Biostatistics, Epidemiology and Informatics (J.K.), University Medical Center, Johannes Gutenberg University Mainz, Germany; Quantitative Neuroimaging Group (C.S.), Academic Unit of Neurology, Biomedical Sciences Institute, Trinity College Dublin, Ireland; Department of Neuropathology (M.N.), University Hospital of Tübingen; and German Center for Neurodegenerative Diseases (DZNE) (M.N.), Tübingen, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Schuster
authors.affiliation: From the Departments of Neurology (J.P.) and Psychosomatic Medicine (E.K., S.T.) and Institute of Forensic Medicine (A.B.), Rostock University Medical Center; German Center for Neurodegenerative Diseases (DZNE) (J.P., S.T.), Rostock; Institute of Medical Biostatistics, Epidemiology and Informatics (J.K.), University Medical Center, Johannes Gutenberg University Mainz, Germany; Quantitative Neuroimaging Group (C.S.), Academic Unit of Neurology, Biomedical Sciences Institute, Trinity College Dublin, Ireland; Department of Neuropathology (M.N.), University Hospital of Tübingen; and German Center for Neurodegenerative Diseases (DZNE) (M.N.), Tübingen, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kasper
authors.affiliation: From the Departments of Neurology (J.P.) and Psychosomatic Medicine (E.K., S.T.) and Institute of Forensic Medicine (A.B.), Rostock University Medical Center; German Center for Neurodegenerative Diseases (DZNE) (J.P., S.T.), Rostock; Institute of Medical Biostatistics, Epidemiology and Informatics (J.K.), University Medical Center, Johannes Gutenberg University Mainz, Germany; Quantitative Neuroimaging Group (C.S.), Academic Unit of Neurology, Biomedical Sciences Institute, Trinity College Dublin, Ireland; Department of Neuropathology (M.N.), University Hospital of Tübingen; and German Center for Neurodegenerative Diseases (DZNE) (M.N.), Tübingen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Büttner
authors.affiliation: From the Departments of Neurology (J.P.) and Psychosomatic Medicine (E.K., S.T.) and Institute of Forensic Medicine (A.B.), Rostock University Medical Center; German Center for Neurodegenerative Diseases (DZNE) (J.P., S.T.), Rostock; Institute of Medical Biostatistics, Epidemiology and Informatics (J.K.), University Medical Center, Johannes Gutenberg University Mainz, Germany; Quantitative Neuroimaging Group (C.S.), Academic Unit of Neurology, Biomedical Sciences Institute, Trinity College Dublin, Ireland; Department of Neuropathology (M.N.), University Hospital of Tübingen; and German Center for Neurodegenerative Diseases (DZNE) (M.N.), Tübingen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Teipel
authors.affiliation: From the Departments of Neurology (J.P.) and Psychosomatic Medicine (E.K., S.T.) and Institute of Forensic Medicine (A.B.), Rostock University Medical Center; German Center for Neurodegenerative Diseases (DZNE) (J.P., S.T.), Rostock; Institute of Medical Biostatistics, Epidemiology and Informatics (J.K.), University Medical Center, Johannes Gutenberg University Mainz, Germany; Quantitative Neuroimaging Group (C.S.), Academic Unit of Neurology, Biomedical Sciences Institute, Trinity College Dublin, Ireland; Department of Neuropathology (M.N.), University Hospital of Tübingen; and German Center for Neurodegenerative Diseases (DZNE) (M.N.), Tübingen, Germany.
authors.forename: Manuela
authors.initials: M
authors.lastname: Neumann
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism / Q000473:pathology* / Q000523:psychology*; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D003071:Cognition; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D009483:Neuropsychological Tests; D011446:Prospective Studies; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology*
chemical_list: D004268:DNA-Binding Proteins; C000598624:TARDBP protein, human