Chronic traumatic encephalopathy neuropathologic change is associated with highest stage limbic-predominant age-related TDP-43 encephalopathy
Year: 2026
Type: article
Study design: Observational Study
Abstract: Traumatic brain injury (TBI) is recognized as a major risk factor for neurodegenerative disease (NDD). Autopsy studies frequently describe chronic traumatic encephalopathy neuropathologic change (CTE-NC) in individuals with histories of repetitive head impact (RHI) exposure, often with accompanying comorbid neurodegenerative proteinopathies. Of these, deposition of abnormally phosphorylated TDP-43 (pTDP-43) has been reported but the prevalence and distribution of pTDP-43 in CTE-NC and its distinction from that encountered in wider NDD are uncertain. Here, patients with a history of RHI and documented NDD (n = 30), and age-matched controls with no known TBI or RHI exposure, either with (n = 24) or without (n = 18) NDD, were identified within the CONNECT-TBI archive. Standardized brain tissue sections stained for pTDP-43 were assessed. pTDP-43 pathology prevalence was similar among RHI patients (40%) and controls with NDD (33%). pTDP-43 was typically localized (limbic-predominant age-related TDP-43 encephalopathy neuropathologic change [LATE-NC] stage 1 to 2) in amygdala and hippocampus in controls with NDD and following RHI exposure without CTE-NC. In contrast, this pathology was often widespread and of high stage (LATE-NC stage 3; P = .0045) in patients with CTE-NC. Thus, CTE-NC may be associated with more widespread pTDP-43 pathology than encountered in aging or those with NDD and no history of TBI/RHI.
DOI: 10.1093/jnen/nlag040
Authors: Hailong Song, Kamar E Ameen-Ali, Claire Kennedy-Dietrich, Jean-Pierre Dolle, Edward B Lee, Douglas H Smith, William Stewart, the CONNECT-TBI Investigators, Etty Cortes, John Crary, Kristin Dams-O’Connor, Ramon Diaz-Arrastia, Brian Edlow, Bruce Fischl, Rebecca Folkerth, Lili-Naz Hazrati, Col Sidney Hinds, Diego Iacono, Victoria Johnson, C Dirk Keene, Julia Kofler, Gabor Kovacs, Geoffrey Manley, David Meaney, Thomas Montine, David Okonkwo, Daniel Perl, John Q Trojanowski, Andre van der Kouwe, Douglas Wiebe, Kristine Yaffe
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,036
Awards: TBI-REPORTER (UK-TBI REpository and data PORTal Enabling discoveRy), CONNECT-TBI, The link between axon damage in traumatic brain injury and tau pathogenesis, G9000004438, G9000076049, G9000084068, G9000118926, G9000250827, Transdisciplinary Research Accelerating Neuropathology Studies and Facilitating Open Research Methods in TBI (TRANSFORM-TBI)
OpenAlex ID: W7155972303