Y. Gu, J. P. Kim, B. H. Kim, H. Lee, J. Lee, H. Kang, S. Yim, D. Shin, H. K. Park, S. Kim, B. H. Lee, J. Lee, H. Kim, H. Zetterberg, M. Y. Chun, D. L. Na, J.-H. Lee, S. H. Cho, B. C. Kim, S. E. Kim, G. Sohn, J. Yun, J.-S. Lim, J. Kim, K. Lee, J. Kim, H. J. Kim, E.-J. Kim, H. Jang, S. W. Seo
Plasma biomarkers of amyloid-associated tau phosphorylation (T1) and established tau proteinopathy (T2) can approximate Alzheimer's 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.