Authors
Dong Wang, Shaozhen Yan, Rongshen Zhou, Yating Li, Lei Liu, Yongbin Wei, Dawei Wang, Hongxiang Yao, Bo Zhou, Jie Lu, Pan Wang, Zhengluan Liao, Yan Chen, Xi Zhang, Ying Han, Chunshui Yu, Kun Zhao, Yong Liu, Alzheimer’s Disease Neuroimaging Initiative
Published in
Science advances. Volume 12. Issue 39. Pages eaef3787. Sep 25, 2026. Epub Sep 23, 2026.
Abstract
Alzheimer's disease is widely conceptualized as a biological continuum initiated by amyloid-β (Aβ) accumulation, followed by tau aggregation and neurodegeneration. Although the ATN framework is commonly used to define disease stages, its static biomarker categories may not fully capture the dynamic pathological transitions that determine the optimal window for anti-Aβ therapies. Here, we introduce a Biological Continuum framework that distinguishes dynamic pathological cascades from static biomarker categories. Using neuroimaging-derived brain network topology, we identify four reproducible subgroups that exhibit distinct biological processes, biomarker signatures, and longitudinal cognitive trajectories. Integrated proteomic analyses suggest that these subgroups reflect sequential molecular transitions corresponding to early vulnerability, initiation, amplification, and terminal stages. Post hoc analysis indicates that slower cognitive decline after amyloid-targeting treatment was observed mainly in the initiation stage group. These findings provide a biologically grounded stratification system that captures disease dynamics overlooked by threshold-based models and offers mechanistic insight into the timing of anti-Aβ therapies.
PMID:
42777020
Bibliographic data and abstract were imported from PubMed on 24 Sep 2026.
Read full publication at:
Please sign in
to see all details.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 34
- Comments 0