ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025
Multimodal spatial gradients to explain regional susceptibility to fibrillar tau in Alzheimer's disease.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Application of the Allen Human Brain Atlas in Alzheimer's disease and Parkinson's disease.Translational neurodegeneration · 2026Review
- Contributions of the Alzheimer's Disease Neuroimaging Initiative to advancing AD research: a targeted review of recent publications.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Multimodal spatial gradients to explain regional susceptibility to fibrillar tau in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
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20 authors.
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Abstract
introductionIn Alzheimer's disease (AD), fibrillar tau gradually progresses from initial seed to larger brain area. However, those brain properties underlying the region-dependent susceptibility to tau accumulation remain unclear.
methodsWe constructed multimodal spatial gradients to characterize molecular properties and connectomic architecture. A predictive model for regional tau deposition was developed by integrating embeddings in the principal gradients of global connectome gradients with gene expression, neurotransmitters, myelin, and amyloid-beta. The model was trained on amyloid-beta-positive participants from Alzheimer's Disease Neuroimaging Initiative (ADNI) and externally validated in independent datasets.
resultsThe combination of gradients explained up to 77.7% of cross-sectional and 77.3% of longitudinal inter-regional variance of tau deposition. Gene set enrichment analysis of a major gene expression gradient points to synaptic transmission to confer increased susceptibility to tau. DISCUSSION: Our findings reveal a spatially heterogeneous molecular landscape shaping regional susceptibility to tau deposition, presenting a powerful system-level explanatory model of tau pathology in AD. HIGHLIGHTS: Spatial gradients of fundamental molecular brain properties associated with tau pathology. The explanatory power showed high consistency across studies. Genetic analyses suggested that synapse expression plays a vital role in tau accumulation.
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