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Spinal Cord Tau and Protein Copathologies Associated With Chronic Traumatic Encephalopathy
Hidetomo Tanaka, Lauren Elaine Black, Shelley L. Forrest, Krisztina Danics, Nusrat Sadia, Mozhgan Khodadadi, Charles Tator, Douglas H. Smith et al.. JAMA Neurology, 2026-01-26
Topic: Brain proteins, microglia and lab models
Of 70 autopsied individuals (62 male, 8 female; mean [SD] age, 64.40 [13.94] years), 20 showed CTE-NC in the brain. All cases with CTE-NC exhibited spinal cord p-tau deposits, especially in cases aged 65 years or older with prior RHI (n = 14), often showing extensive spinal tau pathology as both neuronal (all 14 cases) and astrocytic (12 of 14 cases [86%]) p-tau deposits. Spinal p-tau pathology was associated with microglial activation and motor symptoms. Notably, among the individuals with CTE-NC and prior RHI who were aged 65 years or older, additional spinal protein pathologies were present, comprising p-TDP-43 inclusions (9 of 14 cases [64%]), Aβ deposits (13 of 14 cases [93%]), and α-synuclein deposits (7 of 14 cases [50%]), with all 4 of these pathologies present in 4 individuals (29%). In total, across all 20 CTE-NC cases, p-TDP-43 inclusions were confined to the spinal cord in 5 of the 10 individuals with spinal p-TDP-43 pathology. In contrast, among 50 individuals without CTE-NC, typically sparse p-tau deposits were seen in only 27 (54%). Among the 23 confirmed cases with a history of RHI, 16 (70%) exhibited CTE-NC, while 7 (30%) did not. Spinal tau pathology was more severe in those with CTE-NC; however, astrocytic tau pathology was also present in the group without CTE-NC, unlike in controls without RHI or CTE. Conclusions and Relevance: This case-control study provides autopsy evidence of a high prevalence of complex spinal pathology in individuals with CTE-NC, 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-NC suggests that cumulative trauma might contribute to widespread misfolded protein aggregation.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Tanaka, H., Black, L. E., Forrest, S. L., Danics, K., Sadia, N., Khodadadi, M., et al. (2026). Spinal Cord Tau and Protein Copathologies Associated With Chronic Traumatic Encephalopathy. JAMA Neurology. https://doi.org/10.1001/jamaneurol.2025.5421
Vancouver
Tanaka H, Black LE, Forrest SL, Danics K, Sadia N, Khodadadi M, et al. Spinal Cord Tau and Protein Copathologies Associated With Chronic Traumatic Encephalopathy. JAMA Neurology. 2026. doi:10.1001/jamaneurol.2025.5421. PMID: 41587040.
BibTeX
@article{tanaka2026-41587040,
author = {Tanaka, Hidetomo and Black, Lauren Elaine and Forrest, Shelley L. and Danics, Krisztina and Sadia, Nusrat and Khodadadi, Mozhgan and Tator, Charles and Smith, Douglas H. and others},
title = {{Spinal Cord Tau and Protein Copathologies Associated With Chronic Traumatic Encephalopathy}},
journal = {JAMA Neurology},
year = {2026},
doi = {10.1001/jamaneurol.2025.5421},
pmid = {41587040},
url = {https://doi.org/10.1001/jamaneurol.2025.5421}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- Of 70 autopsied individuals (62 male, 8 female; mean [SD] age, 64.40 [13.94] years), 20 showed CTE-NC in the brain.
- All cases with CTE-NC exhibited spinal cord p-tau deposits, especially in cases aged 65 years or older with prior RHI (n = 14), often showing extensive spinal tau pathology as both neuronal (all 14 cases) and astrocytic (12 of 14 cases [86%]) p-tau deposits.
- Spinal p-tau pathology was associated with microglial activation and motor symptoms.
- Notably, among the individuals with CTE-NC and prior RHI who were aged 65 years or older, additional spinal protein pathologies were present, comprising p-TDP-43 inclusions (9 of 14 cases [64%]), Aβ deposits (13 of 14 cases [93%]), and α-synuclein deposits (7 of 14 cases [50%]), with all 4 of these pathologies present in 4 individuals (29%).
- In total, across all 20 CTE-NC cases, p-TDP-43 inclusions were confined to the spinal cord in 5 of the 10 individuals with spinal p-TDP-43 pathology.
Why it matters
In this autopsy case-control study, all cases with chronic traumatic encephalopathy neuropathologic changes had spinal cord p-tau deposits, often alongside TDP-43, Aβ and α-synuclein deposits, and spinal p-tau was linked to microglial activation and motor symptoms. These are post-mortem observations about co-pathologies and do not provide a treatment or cure.
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Study details
- Study designcase-control study
- Participants14
- Evidence strengthModerate
How this study scored 57/100
Published in a leading specialty journal, and it is a case-control study. Scored zero for effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (JAMA Neurology) |
| Journal's citation record | 2 / 4 | JAMA Neurology: journal h-index 235 (OpenAlex, 2026-10-29) |
| Study design | 6 / 12 | A case-control study |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 1 / 4 | 14 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 3 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 4 / 6 | Cited 13.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 3 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Gábor Géza Kovács: h-index 90 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Toronto: institution h-index 1,923 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 8 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41587040) |
| Free to read | 2 / 2 | Free to read |
| Total | 57 / 100 | — |
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Read the original
- DOI: 10.1001/jamaneurol.2025.5421
- PubMed: 41587040
- Original source →
- Free full text: JAMA Neurology →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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