Plasma eMTBR-tau243 and p-tau205 as T2 biomarkers for biological staging and prognosis in Alzheimer’s disease
Year: 2026
Type: article
Study design: Observational Study
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.
Source: Nature Communications
Authors: Sohyun Yim, Eun Hye Lee, Jungah Lee, Daeun Shin, Heekyoung Kang, Hee Kyung Park, Seonghyeon Kim, Joel B. Braunstein, Philip B. Verghese, Tim West, Matthew R. Meyer, Theresa A. Day, Henrik Zetterberg, Fernando Gonzalez-Ortiz, Nicholas J. Ashton, Tobias Bittner, Annunziata Di Domenico, Gwendlyn Kollmorgen, Hyemin Jang, Jihwan Yun, Min Young Chun, Duk L. Na, Hee Jin Kim, Yuna Gu, Jun Pyo Kim, Sang Won Seo
Institutions: Inje University, Samsung Medical Center, Inje University Haeundae Paik Hospital, Sungkyunkwan University, Indiana University Indianapolis, Indiana University School of Medicine, Soonchunhyang University, Soonchunhyang University Hospital Seoul, Hallym University Chuncheon Sacred Heart Hospital, C2N Diagnostics (United States), Eli Lilly (United States), Sahlgrenska University Hospital, University of Gothenburg, King's College London, South London and Maudsley NHS Foundation Trust, Stavanger University Hospital, F. Hoffmann-La Roche AG, Roche Diagnostics International AG (Switzerland), Asan Medical Center, University of Ulsan, Kyung Hee University, Kyung Hee University Medical Center, Yonsei University, Yonsei University Health System, Yongin Severance Hospital
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: Alzheimer's Association, Alzheimer's Drug Discovery Foundation, Eli Lilly and Company, Familjen Erling-Perssons Stiftelse, Cure Alzheimer's Fund, National Institute for Health and Care Research, University College London, European Commission, Korea Health Industry Development Institute, National Research Foundation of Korea, Hjärnfonden, Vetenskapsrådet, Ministry of Science and ICT, South Korea, UK Dementia Research Institute, Samsung, Avid Radiopharmaceuticals, HORIZON EUROPE Framework Programme, Korea National Institute of Health, Institute for Information and Communications Technology Promotion
Awards: G1057200632, G1153927585, G1451011034, G1451607819, G150733400, G1546555014, G1551449788, G1588116593, G1710774808, G1771944843, G1928552717, G196098375, G201353144, G2057385626, G2081597990, G2157144545, G2256555670, G237833635, G2475953241, G2543812357, G2756832787, G2799940023, G292763017, G3241251457, Fluid biomarkers for neurodegenerative dementias, G3509189227, G3791011679, G3809224024, G3842727039, G3903502641, G4228906844, G4234328627, G4244943609, G4260843567, G4288937912, G4377393254, G4700831490, G4786159458, G490925689, G506008078, Fluid biomarkers for neurodegenerative dementias, G5576250680, G5712520100, CASCADE: CAuSe or Consequence in Alzheimer DiseasE?, G6158734006, G6207287561, G6252389079, G6289970089, G6544145387, G6647163617, Multi-omics Interdisciplinary Research Integration to Address DEmentia diagnosis, G6701856265, G6745400708, G691317373, G7075164165, G7293611571, G7699972493, G7907773732
OpenAlex ID: W7222934409