Plasma eMTBR-tau243 and p-tau205 as T2 biomarkers for biological staging and prognosis in Alzheimer’s disease
Abstract
Plasma biomarkers that reflect distinct stages of Alzheimer’s disease (AD) could enable scalable biological staging. We evaluated phosphorylated tau (p-tau) species across multiple analytical platforms and the endogenously cleaved microtubule-binding region containing residue 243 (eMTBR-tau243) using a dedicated LC-MS/MS platform in a well-characterized cohort with amyloid PET and a subset with tau PET. While T1 biomarkers increased during preclinical stages, eMTBR-tau243 and p-tau205 increased later, consistent with fibrillar tau aggregation. eMTBR-tau243 showed the strongest and stage-dependent associations with regional tau PET and cognition, outperforming T1 biomarkers in predicting cross-sectional and longitudinal cognition. A plasma-based tau staging system integrating p-tau217 and eMTBR-tau243 closely aligned with PET-based tau staging and predicted longitudinal cognitive trajectories. These findings support plasma eMTBR-tau243 as a prototypical T2 biomarker and highlight the potential of plasma-based tau staging for prognosis and therapeutic decision-making in AD.
Related
- Tau PET Braak staging across the Alzheimer Disease continuum using Flortaucipir and MK6240
- Neuropsychiatric symptoms across the revised Alzheimer's disease clinical staging framework: A review of current evidence and implications
- Mapping the evidence on the use of Alzheimer’s disease staging criteria (2011–2026): a scoping review to prioritise action for guidelines – protocol
- A neurocognitive speech taxonomy for voice biomarkers of Alzheimer's disease
- ConvNeXt-KAN: a Kolmogorov-Arnold Network head for robust multi-class staging of Alzheimer's disease from brain MRI.
BibTeX
@article{yim2026plasma,
title = {{Plasma eMTBR-tau243 and p-tau205 as T2 biomarkers for biological staging and prognosis in Alzheimer’s disease}},
author = {Sohyun Yim and Eun Hye Lee and Jungah Lee and Daeun Shin and Heekyoung Kang and Hee Kyung Park and Seonghyeon Kim and Joel B. Braunstein and Philip B. Verghese and Tim West and Matthew R. Meyer and Theresa A. Day and Henrik Zetterberg and Fernando Gonzalez-Ortiz and Nicholas J. Ashton and Tobias Bittner and Annunziata Di Domenico and Gwendlyn Kollmorgen and Hyemin Jang and Jihwan Yun and Min Young Chun and Duk L. Na and Hee Jin Kim and Yuna Gu and Jun Pyo Kim and Sang Won Seo},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78582-x},
url = {https://www.nature.com/articles/s41467-026-78582-x},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Plasma eMTBR-tau243 and p-tau205 as T2 biomarkers for biological staging and prognosis in Alzheimer’s disease
AU - Sohyun Yim
AU - Eun Hye Lee
AU - Jungah Lee
AU - Daeun Shin
AU - Heekyoung Kang
AU - Hee Kyung Park
AU - Seonghyeon Kim
AU - Joel B. Braunstein
AU - Philip B. Verghese
AU - Tim West
AU - Matthew R. Meyer
AU - Theresa A. Day
AU - Henrik Zetterberg
AU - Fernando Gonzalez-Ortiz
AU - Nicholas J. Ashton
AU - Tobias Bittner
AU - Annunziata Di Domenico
AU - Gwendlyn Kollmorgen
AU - Hyemin Jang
AU - Jihwan Yun
AU - Min Young Chun
AU - Duk L. Na
AU - Hee Jin Kim
AU - Yuna Gu
AU - Jun Pyo Kim
AU - Sang Won Seo
PY - 2026
DA - 2026/10/19
JO - Nature Communications
DO - 10.1038/s41467-026-78582-x
UR - https://www.nature.com/articles/s41467-026-78582-x
AB - Plasma biomarkers that reflect distinct stages of Alzheimer’s disease (AD) could enable scalable biological staging. We evaluated phosphorylated tau (p-tau) species across multiple analytical platforms and the endogenously cleaved microtubule-binding region containing residue 243 (eMTBR-tau243) using a dedicated LC-MS/MS platform in a well-characterized cohort with amyloid PET and a subset with tau PET. While T1 biomarkers increased during preclinical stages, eMTBR-tau243 and p-tau205 increased later, consistent with fibrillar tau aggregation. eMTBR-tau243 showed the strongest and stage-dependent associations with regional tau PET and cognition, outperforming T1 biomarkers in predicting cross-sectional and longitudinal cognition. A plasma-based tau staging system integrating p-tau217 and eMTBR-tau243 closely aligned with PET-based tau staging and predicted longitudinal cognitive trajectories. These findings support plasma eMTBR-tau243 as a prototypical T2 biomarker and highlight the potential of plasma-based tau staging for prognosis and therapeutic decision-making in AD.
SN - 2041-1723
ER -