Johannes Prudlo1, Jochem König2, Christina Schuster2, Elisabeth Kasper2, Andreas Büttner2, Stefan Teipel2, Manuela Neumann2. 1. 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. 2. 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.
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.
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: S Shellikeri; V Karthikeyan; R Martino; S E Black; L Zinman; J Keith; Y Yunusova Journal: Neurosci Biobehav Rev Date: 2017-02-02 Impact factor: 8.989
Authors: Ignacio Illán-Gala; Victor Montal; Jordi Pegueroles; Eduard Vilaplana; Daniel Alcolea; Oriol Dols-Icardo; Noemi de Luna; Janina Turón-Sans; Elena Cortés-Vicente; Luis Martinez-Roman; Maria Belén Sánchez-Saudinós; Andrea Subirana; Laura Videla; Isabel Sala; Isabel Barroeta; Sílvia Valldeneu; Rafael Blesa; Jordi Clarimón; Alberto Lleó; Juan Fortea; Ricard Rojas-García Journal: Neurology Date: 2020-09-10 Impact factor: 9.910
Authors: Christopher M Henstridge; Dimitrios I Sideris; Emily Carroll; Sanziana Rotariu; Sally Salomonsson; Makis Tzioras; Chris-Anne McKenzie; Colin Smith; Christine A F von Arnim; Albert C Ludolph; Dorothée Lulé; Danielle Leighton; Jon Warner; Elaine Cleary; Judith Newton; Robert Swingler; Siddharthan Chandran; Thomas H Gillingwater; Sharon Abrahams; Tara L Spires-Jones Journal: Acta Neuropathol Date: 2017-12-22 Impact factor: 17.088
Authors: Jenna M Gregory; Daniel R Whiten; Rebecca A Brown; Teresa P Barros; Janet R Kumita; Justin J Yerbury; Sandeep Satapathy; Karina McDade; Colin Smith; Leila M Luheshi; Christopher M Dobson; Mark R Wilson Journal: Acta Neuropathol Commun Date: 2017-11-07 Impact factor: 7.801
Authors: Rachel H Tan; Yue Yang; Woojin S Kim; Carol Dobson-Stone; John B Kwok; Matthew C Kiernan; Glenda M Halliday Journal: Acta Neuropathol Commun Date: 2017-10-27 Impact factor: 7.801
Authors: Anna G M Temp; Martin Dyrba; Charlotte Büttner; Elisabeth Kasper; Judith Machts; Jörn Kaufmann; Stefan Vielhaber; Stefan Teipel; Johannes Prudlo Journal: Front Neurosci Date: 2021-06-23 Impact factor: 4.677