Brain Region-Specific Epigenomic Reorganization and Altered Cell States in Alzheimer’s Disease

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Alzheimer’s disease (AD) is the most common neurodegenerative disorder, yet the molecular mechanisms underlying its region- and cell-type-specific pathogenesis remain poorly defined. We generated a large-scale, single-cell multi-omic atlas—integrating DNA methylation and 3D genome architecture—from postmortem brain tissue of matched AD patients and cognitively normal controls across three brain regions: the temporal cortex (TC), primary visual cortex (VC), and prefrontal cortex (PFC). Our dataset comprises over 230,000 individual cells and provides a high-resolution view of multi-layer epigenomic regulation in AD.

Recommended citation: Wang W, Berube P, Yang B, Castanon R, Bartlett A, Komandur K, Nery JR, Barragan C, Kenworthy M, Valadon C, Altshul J, Petrella A, Chan D, Chen C, Saldaña Acerbo A, Luo J, Jain M, Soma E, Chen H, Liem M, Marrin M, O'Connor C, Zemke N, Oakley D, Ren B, Hyman BT^#, Ecker JR^#. (2025). "Brain region-specific epigenomic reorganization and altered cell states in Alzheimer's disease." bioRxiv. doi:10.1101/2025.09.29.678849
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