Home › Research › Disease mechanisms
Plasma MTBR-tau243 biomarker identifies tau tangle pathology in Alzheimer’s disease
Kanta Horie, Gemma Salvadó, Rama K. Koppisetti, Shorena Janelidze, Nicolas R. Barthélemy, Yingxin He, Chihiro Sato, Brian Andrew Gordon et al.. Nature Medicine, 2025-03-31
Topic: Brain proteins, microglia and lab models
Insoluble tau aggregates within neurofibrillary tangles are a defining neuropathological feature of Alzheimer’s disease (AD) and closely correlate with clinical symptoms. Although tau pathology can be assessed using tau positron emission tomography, a more accessible biomarker is needed for diagnosis, prognosis and tracking treatment effects. Here we present a new plasma tau species, the endogenously cleaved, microtubule-binding region containing residue 243 (eMTBR-tau243), which specifically reflects tau tangle pathology. Across the AD spectrum in three different cohorts (n = 108, 55 and 739), plasma eMTBR-tau243 levels were significantly elevated at the mild cognitive impairment stage and increased further in dementia. Plasma eMTBR-tau243 showed strong associations with tau positron emission tomography binding (β = 0.72, R2 = 0.56) and cognitive performance (β = 0.60, R2 = 0.40), outperforming other plasma tau (%p-tau217 and %p-tau205) biomarkers. These results suggest that plasma eMTBR-tau243 may be useful for estimating the tauopathy load in AD, thereby improving the diagnostic evaluation of AD in clinical practice and monitoring the efficacy of tau-targeted therapies in clinical trials. Plasma eMTBR-tau243 is a specific biomarker of tau tangles in Alzheimer’s disease and enables the detecting and tracking of Alzheimer’s clinical impairment.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Horie, K., Salvadó, G., Koppisetti, R. K., Janelidze, S., Barthélemy, N. R., He, Y., et al. (2025). Plasma MTBR-tau243 biomarker identifies tau tangle pathology in Alzheimer’s disease. Nature Medicine. https://doi.org/10.1038/s41591-025-03617-7
Vancouver
Horie K, Salvadó G, Koppisetti RK, Janelidze S, Barthélemy NR, He Y, et al. Plasma MTBR-tau243 biomarker identifies tau tangle pathology in Alzheimer’s disease. Nature Medicine. 2025. doi:10.1038/s41591-025-03617-7. PMID: 40164726.
BibTeX
@article{horie2025-40164726,
author = {Horie, Kanta and Salvadó, Gemma and Koppisetti, Rama K. and Janelidze, Shorena and Barthélemy, Nicolas R. and He, Yingxin and Sato, Chihiro and Gordon, Brian Andrew and others},
title = {{Plasma MTBR-tau243 biomarker identifies tau tangle pathology in Alzheimer’s disease}},
journal = {Nature Medicine},
year = {2025},
doi = {10.1038/s41591-025-03617-7},
pmid = {40164726},
url = {https://doi.org/10.1038/s41591-025-03617-7}
}
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
- Across the AD spectrum in three different cohorts (n = 108, 55 and 739), plasma eMTBR-tau243 levels were significantly elevated at the mild cognitive impairment stage and increased further in dementia.
- These results suggest that plasma eMTBR-tau243 may be useful for estimating the tauopathy load in AD, thereby improving the diagnostic evaluation of AD in clinical practice and monitoring the efficacy of tau-targeted therapies in clinical trials.
Why it matters
In three cohorts, plasma eMTBR-tau243 was elevated at the mild cognitive impairment stage and increased further in dementia, and it was strongly associated with tau PET binding and cognitive performance, outperforming other plasma tau biomarkers. This is a blood biomarker for detecting and tracking tau tangles, not a treatment, cure or prevention.
Study details
- Participants108
- Evidence strengthLow
How this study scored 67/100
Published in a top-tier journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (Nature Medicine) |
| Journal's citation record | 4 / 4 | Nature Medicine: journal h-index 763 (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 | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 108 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 | 5 / 7 | Cited 125 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 41.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 6 / 6 | Cited 68.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 16 other studies in this library |
| Still being cited | 3 / 4 | Cited 125 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Randall John Bateman: h-index 101 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Washington University in St. Louis: institution h-index 1,962 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 8 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40164726) |
| Free to read | 2 / 2 | Free to read |
| Total | 67 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1038/s41591-025-03617-7
- PubMed: 40164726
- Original source →
- Free full text: Nature Medicine →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 20.
Later studies that cite this one
16 studies in the alzhub library list this one in their references. Showing the 8 highest-scoring.
Related studies in Disease mechanisms
Also tagged “phosphorylated”
732 studies in the library carry the topic tag “phosphorylated”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 732 tagged studies.