Multimodal spatial gradients to explain regional susceptibility to fibrillar tau in Alzheimer's disease
Alzheimer's & Dementia, vol 21, issue 7, pp e70170. · May 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