A study published in the journal Science has revealed a previously unknown biological factor in Alzheimer's disease: the three-dimensional organization of the genome in individual brain cells of patients differs significantly from normal, reports infohub.kz.
The discovery was made by a team of scientists from Carnegie Mellon University, the University of Pittsburgh School of Medicine, and the University of Washington. As ScienceDaily writes, the use of artificial intelligence methods allowed them to detect blurring of chromatin boundaries in brain cells, opening new avenues for treating the disease.
The team, led by Professor Jian Ma and Associate Professor Hansruedi Mathys, examined samples of the prefrontal cortex from deceased donors. Using the GAGE-seq method, the researchers simultaneously measured gene expression and three-dimensional genome contacts in individual cells, then compared the data with spatial tissue maps. An AI model called Hicformer was used to analyze the relationships.
The analysis showed that in Alzheimer's disease, the boundaries between active and inactive regions of the genome become blurred — so-called "increased compartment mixing" — nearby DNA interactions decrease, and the connection between genes and regulatory elements weakens. These chromatin structure disruptions are associated with reduced activity of neuronal and synaptic genes, metabolic changes, and a stressed state of microglia.
According to the authors, the 3D reorganization of the genome represents an important layer of Alzheimer's pathology affecting millions of people and could become a target for developing new treatments.