Scientists find new Alzheimer's layer in genome's 3D structure

September 13, 2026 at 07:02 PM2 min

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Researchers at Carnegie Mellon, the University of Pittsburgh, and the University of Washington found that the three-dimensional organization of the genome differs in certain brain cells from people with Alzheimer's disease. The study, published in Science, linked these changes in genome folding to shifts in gene activity and brain tissue organization. The team combined single-cell technology, spatial mapping, and a deep learning model to build the picture.

Key Facts

The study was published in Science and involved researchers from Carnegie Mellon University, the University of Pittsburgh, and the University of Washington.
Researchers examined postmortem samples from the prefrontal cortex of people with and without Alzheimer's disease who had participated in a long-term dementia study.
The team used GAGE-seq, a technique that measures both gene expression and three-dimensional genome contacts within the same individual cell.
Jian Ma, the Ray and Stephanie Lane Professor of Computational Biology at Carnegie Mellon, led and supervised the study.
Hansruedi Mathys, assistant professor of neurobiology at the University of Pittsburgh, directed the Pitt arm of the study.

Genome Folding Differences

The three-dimensional organization of the genome differs in certain brain cells from people with Alzheimer's disease. These changes in genome folding were connected with shifts in gene activity and the organization of brain tissue. DNA folds into a complex three-dimensional structure that helps determine which genes are accessible and active. Changes in that physical organization can influence how cells function.

Research Methods

The team combined single-cell technology, spatial mapping of brain tissue, and a newly developed deep learning model. GAGE-seq measurements were combined with spatial transcriptomic maps, which preserve information about where gene activity occurs within intact brain tissue. By bringing these datasets together, the researchers connected the physical organization of the genome with gene regulation while also seeing where Alzheimer's related molecular and cellular changes appeared within the surrounding tissue.

Study Leadership

Jian Ma, the Ray and Stephanie Lane Professor of Computational Biology at Carnegie Mellon, led and supervised the study. Hansruedi Mathys, assistant professor of neurobiology at the University of Pittsburgh, directed the Pitt arm of the study. The study involved scientists from Carnegie Mellon's Ray and Stephanie Lane Computational Biology Department, Pitt's Department of Neurobiology, and collaborating institutions.