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Plasma MTBR-tau243 biomarker identifies tau tangle pathology in Alzheimer's disease

Horie, Kanta ; Salvadó, Gemma LU ; Koppisetti, Rama K ; Janelidze, Shorena LU ; Barthélemy, Nicolas R ; He, Yingxin ; Sato, Chihiro ; Gordon, Brian A ; Jiang, Hong and Benzinger, Tammie L S , et al. (2025) In Nature Medicine
Abstract

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... (More)

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.

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Contribution to journal
publication status
epub
subject
in
Nature Medicine
publisher
Nature Publishing Group
external identifiers
  • pmid:40164726
ISSN
1546-170X
DOI
10.1038/s41591-025-03617-7
language
English
LU publication?
yes
additional info
© 2025. The Author(s).
id
b956bcb3-9b43-45a8-866d-8186842e96ee
date added to LUP
2025-04-02 09:00:50
date last changed
2025-04-04 14:30:15
@article{b956bcb3-9b43-45a8-866d-8186842e96ee,
  abstract     = {{<p>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.</p>}},
  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 A and Jiang, Hong and Benzinger, Tammie L S and Stomrud, Erik and Holtzman, David M and Mattsson-Carlgren, Niklas and Morris, John C and Palmqvist, Sebastian and Ossenkoppele, Rik and Schindler, Suzanne E and Hansson, Oskar and Bateman, Randall J}},
  issn         = {{1546-170X}},
  language     = {{eng}},
  month        = {{03}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Medicine}},
  title        = {{Plasma MTBR-tau243 biomarker identifies tau tangle pathology in Alzheimer's disease}},
  url          = {{http://dx.doi.org/10.1038/s41591-025-03617-7}},
  doi          = {{10.1038/s41591-025-03617-7}},
  year         = {{2025}},
}