Mining Alzheimer's Interactomes, Macromolecular Complexes and Pathways for drug discovery
Kalpana Panneerselvam, Krishna Kumar Tiwari, Luana Licata, Simona Panni, Sylvie Ricard‐Blum, Sucharitha Balu, Susie Huget, Juan Jose Medina Reyes, Eliot Ragueneau, Livia Perfetto, Birgit Meldal, Sandra E. Orchard, Henning Hermjakob · 2025
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that leads to dementia. Many cases are diagnosed annually and there is no currently available cure. Understanding the underlying disease biology of AD through the study of molecular networks, particularly by mapping clinical variants to tissue-specific interactomes and regulatory macromolecular assemblies, offers a promising avenue to elucidate altered disease pathways. This, in turn, could provide valuable insights for drug discovery. In this study, we leverage our manually curated AD-specific dataset from the IMEx consortium, which provides detailed interaction data, including the relationship between interacting partners, detection in specific host tissues and cell lines, and the impact of variants on interaction outcomes. By integrating these data with information on protein complex composition taken from the Complex Portal, we have identified relevant macromolecular assemblies enriched in AD networks. Further pathway enrichment analysis is conducted using Reactome, enabling a comprehensive exploration of disease mechanisms and potential therapeutic targets.