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Neurology. 2016 Sep 6;87(10):1019-23. doi: 10.1212/WNL.0000000000003062. Epub 2016 Aug 3.

TDP-43 pathology and cognition in ALS: A prospective clinicopathologic correlation study.

Author information

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.

PMID:
27488596
DOI:
10.1212/WNL.0000000000003062
[Indexed for MEDLINE]

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