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MC1 detects tau pathology in chronic traumatic encephalopathy
Eleanor Clifton-Bligh, Andrew J. Affleck, Jennifer E. Cropley, Maggie Lee, Karina Hammond, Catherine M. Suter, Michael Edward Buckland, Margaret Sunde. Journal of Neuropathology & Experimental Neurology, 2026-03-02
Topic: Brain proteins, microglia and lab models
To the Editor: MC1 is a monoclonal anti-tau antibody developed by the Peter Davies laboratory in the 1990s to aid the neuropathological diagnosis of Alzheimer disease (AD).1 Raised against Alz-50-immunopurified paired helical filaments (PHFs) from an AD brain, MC1 recognizes a conformational, discontinuous epitope involving residues 7-9 in the N-terminus and 313-322 in the third repeat domain of tau (Figure 1A). This epitope reflects an abnormal folding of tau that occurs among the earliest structural alterations in AD, preceding PHF formation.2 In a recent letter to this journal from Sorrentino and colleagues, it was proposed that immunohistochemistry (IHC) with MC1 could be used to distinguish the tau pathology of AD from that of chronic traumatic encephalopathy (CTE).3 CTE is a tauopathy that is uniquely associated with exposure to repeated head injury and therefore likely involves mechanisms of tau accumulation distinct from those of AD.4 Cryo-EM has revealed that the ultrastructural conformation of tau PHFs differs between AD and CTE,5 and this may represent a point of difference for diagnostic purposes. Sorrentino and colleagues reported, albeit with a limited number of cases, that MC1 could readily detect tau aggregates in AD, but not in CTE.3 Their finding raises the possibility that MC1 immunoreactivity might distinguish a unique tau structure and be an important tool for exclusion of CTE. To further investigate this, we assessed MC1 immunoreactivity in a larger cohort of CTE cases from the Australian Sports Brain Bank. We included both cases with pure CTE, and CTE cases with co-morbid AD pathology (Table 1).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Clifton-Bligh, E., Affleck, A. J., Cropley, J. E., Lee, M., Hammond, K., Suter, C. M., et al. (2026). MC1 detects tau pathology in chronic traumatic encephalopathy. Journal of Neuropathology & Experimental Neurology. https://doi.org/10.1093/jnen/nlag011
Vancouver
Clifton-Bligh E, Affleck AJ, Cropley JE, Lee M, Hammond K, Suter CM, et al. MC1 detects tau pathology in chronic traumatic encephalopathy. Journal of Neuropathology & Experimental Neurology. 2026. doi:10.1093/jnen/nlag011. PMID: 41802149.
BibTeX
@article{cliftonbligh2026-41802149,
author = {Clifton-Bligh, Eleanor and Affleck, Andrew J. and Cropley, Jennifer E. and Lee, Maggie and Hammond, Karina and Suter, Catherine M. and Buckland, Michael Edward and Sunde, Margaret},
title = {{MC1 detects tau pathology in chronic traumatic encephalopathy}},
journal = {Journal of Neuropathology \& Experimental Neurology},
year = {2026},
doi = {10.1093/jnen/nlag011},
pmid = {41802149},
url = {https://doi.org/10.1093/jnen/nlag011}
}
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Key findings
- This epitope reflects an abnormal folding of tau that occurs among the earliest structural alterations in AD, preceding PHF formation.2 In a recent letter to this journal from Sorrentino and colleagues, it was proposed that immunohistochemistry (IHC) with MC1 could be used to distinguish the tau pathology of AD from that of chronic traumatic encephalopathy (CTE).3 CTE is a tauopathy that is uniquely associated with exposure to repeated head injury and therefore likely involves mechanisms of tau accumulation distinct from those of AD.4 Cryo-EM has revealed that the ultrastructural conformation of tau PHFs differs between AD and CTE,5 and this may represent a point of difference for diagnostic purposes.
Why it matters
This letter discusses whether the MC1 antibody can detect tau pathology in chronic traumatic encephalopathy, a condition linked to repeated head injury. It is about a diagnostic tool for distinguishing tau diseases and does not address treating, curing or preventing Alzheimer's disease.
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Study details
- Evidence strengthModerate
How this study scored 34/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Neuropathology & Experimental Neurology) |
| Journal's citation record | 2 / 4 | Journal of Neuropathology & Experimental Neurology: journal h-index 239 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| 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 | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 0 / 7 | Cited 0 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.0 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 0 / 6 | Cited 0.0× 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 | 0 / 4 | Cited 0 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Margaret Sunde: h-index 62 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | The University of Sydney: institution h-index 1,466 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41802149) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 34 / 100 | — |
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