3D brain map shows how Alzheimer’s disrupts DNA

Researchers used a technique that simultaneously measures the spatial organisation of DNA and which genes are active in single cells. This approach is called single-cell multiomics. They found that cells in Alzheimer’s brains not only function differently but that their DNA is also folded differently. That change in 3D structure is linked to abnormal gene activity.

The study, published in Science, shows that these structural changes are specific to each cell type. Neurons, support cells and brain immune cells each display a distinct pattern. The researchers connected these abnormalities to genes previously associated with Alzheimer’s, now seen for the first time in a spatial context.

What does 3D structure mean in practice?

Think of DNA as a long thread crammed into a tiny ball. How that thread is folded determines which sections are accessible to the molecular machinery that reads genes. When the folding changes, which genes are active changes too. In Alzheimer’s, this folding appears to shift systematically in specific cell types, altering their activity in turn.

Changes appear earlier than expected

One striking finding is that some structural changes in the genome (the full set of genetic material in a cell) appear before classic disease symptoms become visible. This suggests the disease may begin smouldering at the molecular level long before someone notices memory problems. Whether this is clinically useful for early detection requires further study. The authors present this as a descriptive insight, not a proven diagnostic tool.

The method itself is also significant. Single-cell multiomics enables researchers to build unprecedentedly detailed maps of disease processes, potentially accelerating future research into Alzheimer’s and other brain diseases.

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