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Immunohistochemical staining of pTDP-43 and HLA-DR-defined microglial activation was semi-quantitatively assessed in grey and\/or white matter of the prefrontal cortex, thalamus, hippocampus, and motor cortex.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fourteen patients had pure motor ALS, four patients had ALSci\/bi, and three patients had ALS-bvFTD. pTDP-43 pathology in the grey matter of the prefrontal cortex and\n                      <jats:italic>gyrus dentatus<\/jats:italic>\n                      differed between groups, especially between pure motor ALS and ALS-bvFTD. For each extra-motor brain region, pTDP-43 severity was highest in patients with ALS-bvFTD and lowest in patients with pure motor ALS, with ALSci\/bi in between. This pattern was not observed for microglial activation. Associations between white matter pTDP-43 severity and cognitive\/behavioural impairment were less robust than those in grey matter.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Severity of cognitive and\/or behavioural impairment in ALS is related to severity of pTDP-43 pathology, in particular in the grey matter of extra-motor brain regions; we did not detect a clear association with microglial activation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00415-026-13848-4","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T18:27:11Z","timestamp":1778869631000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Associations of cognitive and behavioural impairment in ALS with brain pathology: pTDP-43 versus microglial activation"],"prefix":"10.1007","volume":"273","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2118-6356","authenticated-orcid":false,"given":"Hanneke M. 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