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Tau filaments in AD adopt the \u201cAlzheimer\u2019s fold\u201d, which is distinct from other tauopathies and highly conserved across sporadic and familial AD. However, to date, structural studies have focused on pure AD, despite the high prevalence of comorbid pathologies. In particular, up to half of AD patients harbor limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC). This co-pathology\u2014 consisting of mislocalized and aggregated TDP-43, mainly restricted to the medial temporal lobe\u2014is associated with accelerated clinical decline and more severe tau pathology. Whether there is a structural basis for this clinical synergy remains unknown. Here, using cryo-electron microscopy, we determine the structure of tau filaments from three AD patients with LATE-NC. We show that in addition to the expected Alzheimer\u2019s fold tau filaments, all cases exhibit a distinct fibril morphology identical to chronic traumatic encephalopathy (CTE) fold tau. Additional sampling revealed CTE neuropathology in one patient, suggestive features without definitive CTE in the second, and no evidence of CTE in the third. These findings raise questions about the relationship between LATE-NC and CTE, the effect of TDP-43 on tau conformation, and the etiology of LATE-NC.<\/jats:p>","DOI":"10.1101\/2025.10.21.683735","type":"posted-content","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T02:00:15Z","timestamp":1761184815000},"source":"Crossref","is-referenced-by-count":2,"title":["CTE-Type Tau Filaments in Alzheimer\u2019s Disease with Co-morbid LATE-NC"],"prefix":"10.64898","author":[{"given":"Jaimin K.","family":"Rana","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emile S.","family":"Pinarbasi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin 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