Spinal Cord Tau and Protein Copathologies Associated With Chronic Traumatic Encephalopathy.
Older chronic traumatic encephalopathy cases often show multiple spinal protein pathologies together.
Spinal Cord Tau and Protein Copathologies Associated With Chronic Traumatic Encephalopathy.
IMPORTANCE: Exposure to repetitive head impacts (repetitive head impacts) is associated with increased risk of a range of neurodegenerative diseases, including Alzheimer disease and amyotrophic lateral sclerosis.
To evaluate spinal cord pathologies associated with repetitive head impacts exposure or chronic traumatic encephalopathy neuropathologic change (chronic traumatic encephalopathy-NC) in the brain.
DESIGN, SETTING, AND PARTICIPANTS: This case-control study of a retrospective autopsy series (June 2019 to August 2025) was performed among autopsied individuals who served as repetitive head impacts-exposed cases or controls in a multicenter brain bank collaboration.
Of 70 autopsied individuals (62 male, 8 female; mean [SD] age, 64.40 [13.94] years), 20 showed CTE neuropathologic change in the brain.
All cases with CTE neuropathologic change exhibited spinal cord p-tau deposits, especially in cases aged 65 years or older with prior repetitive head impacts (n = 14), often showing extensive spinal tau pathology as both neuronal (all 14 cases) and astrocytic (12 of 14 cases [86%]) p-tau deposits.
This case-control study provides autopsy evidence of a high prevalence of complex spinal pathology in individuals with CTE neuropathologic change, supporting the concept of trauma-related encephalomyelopathy.
The frequent co-occurrence of p-TDP-43, Aβ, and α-synuclein pathologies in individuals aged 65 years or older with CTE neuropathologic change suggests that cumulative trauma might contribute to widespread misfolded protein aggregation.