Study reveals disrupted 3D genome architecture as a new layer in Alzheimer's disease
Researchers found that the three-dimensional folding of DNA is altered in several brain cell types of Alzheimer’s patients, linking these structural changes to gene activity.
Scientists from Carnegie Mellon University's School of Computer Science, the University of Pittsburgh School of Medicine and the University of Washington integrated single-cell sequencing, spatial transcriptomics and a deep-learning framework called Hicformer to examine DNA's three-dimensional organization in the prefrontal cortex of individuals with Alzheimer’s disease. Their analysis showed that genome compartments become less sharply defined, with increased "compartment mingling," fewer short-range contacts and more distant interactions.
These architectural shifts were tied to lower overall gene activity, especially in neuronal and synaptic pathways, and to altered metabolic, stress-response and senescence-related programs in microglia. The findings position chromatin folding as a new layer of Alzheimer’s biology, providing a platform to test whether specific structural changes drive disease progression and could become therapeutic targets. The work appears in Science and was supported by NIH funding.
Why it matters
Understanding genome folding in Alzheimer’s adds a potential target for future treatments of a disease affecting millions.
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