Year: 2026
Type: preprint
Study design: Observational Study
Abstract: 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.
Source: medRxiv
Authors: Yuna Gu, Jun Pyo Kim, Bo Hyun Kim, Hyunwoo Lee, Jungah Lee, Heekyoung Kang, Sohyun Yim, Daeun Shin, Hee Kyung Park, Seonghyeon Kim, Byung Hwa Lee, Jeongha Lee, Hyeongjin Kim, Henrik Zetterberg, Min Young Chun, Duk L. Na, Jae-Hong Lee, Soo Hyun Cho, Byeong C. Kim, Si Eun Kim, Gyeongmo Sohn, Jihwan Yun, Jae-Sung Lim, Juyoung Kim, Kyungbok Lee, Jaeho Kim, Hee Jin Kim, Eun-Joo Kim, Hyemin Jang, Sang Won Seo
Institutions: Samsung Medical Center, Sungkyunkwan University, Hallym University Dongtan Sacred Heart Hospital, Chonnam National University, Chonnam National University Hospital, Asan Medical Center, University of Ulsan, Inje University Haeundae Paik Hospital, Sahlgrenska University Hospital, UK Dementia Research Institute, UCL Queen Square Institute of Neurology, University College London, University of Gothenburg, Yonsei University, Yonsei University Health System, Yongin Severance Hospital, Kyung Hee University Medical Center, Pusan National University Hospital, Pusan National University
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Alzheimer's Association, Familjen Erling-Perssons Stiftelse, Cure Alzheimer's Fund, Stiftelsen för Gamla Tjänarinnor, European Commission, Korea Health Industry Development Institute, Hjärnfonden, Vetenskapsrådet, Ministry of SMEs and Startups, Ministry of Science and ICT, South Korea, Advanced Research Projects Agency, HORIZON EUROPE Framework Programme, Korea National Institute of Health
Awards: G1451607819, G150733400, G1546555014, G1588116593, G1710774808, G1771944843, G1833008592, G1928552717, G201353144, G2081597990, G2256555670, G237833635, G2475953241, Fluid biomarkers for neurodegenerative dementias, G3509189227, G3791011679, G3809224024, G3842727039, G4228906844, G4244943609, G4260843567, G4345004521, Fluid biomarkers for neurodegenerative dementias, G5576250680, G5712520100, CASCADE: CAuSe or Consequence in Alzheimer DiseasE?, G6158734006, G6252389079, G6701856265, G691317373, G7293611571, G7907773732
OpenAlex ID: W7213261286