Plasma proteomics reveals stage-dependent biological remodelling in Alzheimer's disease
- 1Samsung Medical Center; Sungkyunkwan University School of Medicine
Abstract
Plasma biomarkers of amyloid-associated tau phosphorylation (T1) and established tau proteinopathy (T2) can approximate Alzheimers disease stage, but whether plasma-defined stages correspond to broader biological states is unknown. In 1,035 participants from a multicentre Korean cohort, we used a 220-plex immunoassay platform to compare T1/T2 biomarkers against amyloid and tau positron emission tomography anchors and construct a five-stage framework. Brain-derived phosphorylated tau 217 and endogenously cleaved microtubule-binding-region tau formed the parsimonious backbone. Baseline stage ordered Clinical Dementia Rating-Sum of Boxes trajectories, and forward within-person stage movement was associated with faster clinical worsening. Among 197 non-tau proteins, 34 were stage-associated; the T1-positive transition showed the broadest proteomic shift, with more selective remodelling later. In serial samples, 15 proteins changed longitudinally, with 13 recapitulating the cross-sectional stage pattern. Thus, plasma-defined disease position mapped onto distinct, partly dynamic biological states beyond the defining T1/T2 biomarkers.
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BibTeX
@misc{gu2026plasma,
title = {{Plasma proteomics reveals stage-dependent biological remodelling in Alzheimer's disease}},
author = {Y. Gu and J. P. Kim and B. H. Kim and H. Lee and J. Lee and H. Kang and S. Yim and D. Shin and H. K. Park and S. Kim and B. H. Lee and J. Lee and H. Kim and H. Zetterberg and M. Y. Chun and D. L. Na and J.-H. Lee and S. H. Cho and B. C. Kim and S. E. Kim and G. Sohn and J. Yun and J.-S. Lim and J. Kim and K. Lee and J. Kim and H. J. Kim and E.-J. Kim and H. Jang and S. W. Seo},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.14.26362968},
url = {https://www.medrxiv.org/content/10.64898/2026.09.14.26362968v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Plasma proteomics reveals stage-dependent biological remodelling in Alzheimer's disease
AU - Y. Gu
AU - J. P. Kim
AU - B. H. Kim
AU - H. Lee
AU - J. Lee
AU - H. Kang
AU - S. Yim
AU - D. Shin
AU - H. K. Park
AU - S. Kim
AU - B. H. Lee
AU - J. Lee
AU - H. Kim
AU - H. Zetterberg
AU - M. Y. Chun
AU - D. L. Na
AU - J.-H. Lee
AU - S. H. Cho
AU - B. C. Kim
AU - S. E. Kim
AU - G. Sohn
AU - J. Yun
AU - J.-S. Lim
AU - J. Kim
AU - K. Lee
AU - J. Kim
AU - H. J. Kim
AU - E.-J. Kim
AU - H. Jang
AU - S. W. Seo
PY - 2026
DA - 2026/09/14
PB - medRxiv
DO - 10.64898/2026.09.14.26362968
UR - https://www.medrxiv.org/content/10.64898/2026.09.14.26362968v1
AB - Plasma biomarkers of amyloid-associated tau phosphorylation (T1) and established tau proteinopathy (T2) can approximate Alzheimers disease stage, but whether plasma-defined stages correspond to broader biological states is unknown. In 1,035 participants from a multicentre Korean cohort, we used a 220-plex immunoassay platform to compare T1/T2 biomarkers against amyloid and tau positron emission tomography anchors and construct a five-stage framework. Brain-derived phosphorylated tau 217 and endogenously cleaved microtubule-binding-region tau formed the parsimonious backbone. Baseline stage ordered Clinical Dementia Rating-Sum of Boxes trajectories, and forward within-person stage movement was associated with faster clinical worsening. Among 197 non-tau proteins, 34 were stage-associated; the T1-positive transition showed the broadest proteomic shift, with more selective remodelling later. In serial samples, 15 proteins changed longitudinally, with 13 recapitulating the cross-sectional stage pattern. Thus, plasma-defined disease position mapped onto distinct, partly dynamic biological states beyond the defining T1/T2 biomarkers.
ER -