Scientists find a new layer of Alzheimer’s hidden in the genome

Scientists found that the 3D organization of DNA is disrupted in several types of brain cells affected by Alzheimer’s disease, altering how important genes are switched on and off. The discovery reveals a previously underexplored layer of the disease that could open new paths for understanding and eventually treating Alzheimer’s. Scientists find a new layer of Alzheimer’s hidden in the genome.

The study, published in Science, found that the three-dimensional organization of the genome differs in certain brain cells from people with Alzheimer’s disease. Scientists from SCS’s Ray and Stephanie Lane Computational Biology Department, Pitt’s Department of Neurobiology, and collaborating institutions connected these changes in genome folding with shifts in gene activity and the organization of brain tissue. To build this detailed picture, the team combined single-cell technology, spatial mapping of brain tissue, and a newly developed deep learning model.

Looking Beyond Amyloid and Tau "Alzheimer’s disease cannot be understood one layer at a time," said Jian Ma, the Ray and Stephanie Lane Professor of Computational Biology who led and supervised the study. "The genome’s 3D structure is a fundamental regulatory layer that helps to connect DNA sequence to gene activity. By integrating genome folding, cell state, and tissue context, we can move beyond cataloging disease-associated changes toward understanding how they fit together and which mechanisms to test next." DNA does not sit inside a cell as a simple straight strand.