Authors
Yating Li, Dong Wang, Rongshen Zhou, Shaozhen Yan, Dawei Wang, Yongbin Wei, Hongxiang Yao, Bo Zhou, Jie Lu, Pan Wang, Zhengluan Liao, Ying Han, Xi Zhang, Yihe Zhang, Yong Liu, Kun Zhao, Alzheimer's Disease Neuroimaging Initiative
Published in
Alzheimer's & dementia : the journal of the Alzheimer's Association. Volume 22. Issue 7. Pages e71638.
Abstract
Mild cognitive impairment (MCI), a prodromal stage of Alzheimer's disease (AD), shows pronounced clinical heterogeneity poorly explained by pathology burden, representing a gap complicating prognosis. As the brain operates as a complex network for information integration, we hypothesized that connectome architecture mediates the link between AD pathology and clinical expression.
We developed a framework integrating structural and functional connectomes from multi-center cohorts, performing connectome-based subtyping in MCI, with analyses of upstream pathology, downstream phenotypes, and transcriptomic associations.
This approach identified an "MCI-compromised" (MCI-C) subgroup characterized by extensive structural-functional connectomic disruption and an "MCI-preserved" (MCI-P) subgroup with relatively preserved connectome integrity. Despite comparable pathology, MCI-C demonstrated more severe neurodegeneration, accelerated cognitive decline, and elevated progression risk. Multiscale analyses linked these patterns to transcriptomic profiles of mitochondrial, synaptic, and neuroimmune processes.
These findings demonstrate that the connectome acts as a critical mediator, rather than a passive endophenotype, shaping AD clinical expression.
PMID:
42381349
Bibliographic data and abstract were imported from PubMed on 01 Jul 2026.
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