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

• Published in: Neurology Vol. 87; no. 10; p. 1019
• Main Authors: Prudlo, Johannes, König, Jochem, Schuster, Christina, Kasper, Elisabeth, Büttner, Andreas, Teipel, Stefan, Neumann, Manuela
• Format: Journal Article
• Language: English
• Published: United States 06.09.2016
• Subjects: Aged; Amyotrophic Lateral Sclerosis - metabolism; Amyotrophic Lateral Sclerosis - pathology; Amyotrophic Lateral Sclerosis - psychology; Brain - metabolism; Brain - pathology; Cognition; DNA-Binding Proteins - metabolism; Humans; Middle Aged; Neuropsychological Tests; Prospective Studies; Severity of Illness Index; Spinal Cord - metabolism; Spinal Cord - pathology
• ISSN: 1526-632X
• DOI: 10.1212/WNL.0000000000003062

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. 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. 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. Our data suggest a distinct dynamic of TDP-43 progression and distribution in ALS-FTD in contrast to ALS without FTD.