Multimodal spatial gradients to explain regional susceptibility to fibrillar tau in Alzheimer's disease
Published in Alzheimer's & Dementia, vol 21, issue 7, pp e70170., 2025
This study investigates multimodal spatial gradients to characterize molecular properties and connectomic architecture in Alzheimer’s disease (AD), aiming to understand the regional differences in fibrillar tau accumulation. A predictive model for regional tau deposition was developed by integrating connectome gradients with gene expression, neurotransmitters, myelin, and amyloid-beta. The model, trained on amyloid-beta-positive participants, demonstrates a significant ability to explain the variance in tau deposition. Gene set enrichment analysis suggests a role for synaptic transmission in conferring increased susceptibility to tau. The findings reveal a spatially heterogeneous molecular landscape that shapes how tau pathology affects different brain regions in AD.
Recommended citation: Luan, Y., Zheng, L., Denecke, J., Dehsarvi, A., Roemer-Cassiano, S. N., Dewenter, A., Steward, A., Shcherbinin, S., Otero Svaldi, D., Kotari, V., Higgins, I. A., Pontecorvo, M. J., Valentim, C., Schnabel, J. A., Casale, F. P., Dyrba, M., Teipel, S., Franzmeier, N., & Ewers, M. (2025). Multimodal spatial gradients to explain regional susceptibility to fibrillar tau in Alzheimer’s disease. Alzheimer’s & Dementia, 21(7), e70170. https://doi.org/10.1002/alz.70170
Recommended citation: Luan, Y., Zheng, L., Denecke, J., Dehsarvi, A., Roemer-Cassiano, S. N., Dewenter, A., Steward, A., Shcherbinin, S., Otero Svaldi, D., Kotari, V., Higgins, I. A., Pontecorvo, M. J., Valentim, C., Schnabel, J. A., Casale, F. P., Dyrba, M., Teipel, S., Franzmeier, N., & Ewers, M. (2025). Multimodal spatial gradients to explain regional susceptibility to fibrillar tau in Alzheimer's disease. Alzheimer's & Dementia, 21(7), e70170. https://doi.org/10.1002/alz.70170
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