A single-cell multiomics study connected genome 3D architecture changes to disrupted gene regulation in Alzheimer’s disease, offering a mechanistic layer beyond standard transcriptomics. Researchers reported in Science that postmortem prefrontal cortex samples from Alzheimer’s patients showed widespread alterations in chromatin organization, including reduced short-range interactions and increased longer-range interactions, plus weakened promoter-proximal interactions. The work used GAGE-seq to measure gene expression and physical genome contacts in the same cells, with AI modeling (including Hicformer) integrating sequence and 3D genome features. The study’s maps across cell types may help prioritize targets tied to regulatory element disruption and microglia senescence-related activation in neurodegeneration programs.