Some people have plenty of Alzheimer’s pathology in their brains and still keep their cognition. In a new medRxiv preprint, graduate student Collin Spencer built a cell-type-resolved gene regulatory network atlas from 1.7 million nuclei across 687 people and 26 cell types in the prefrontal cortex. Each person was classified as a control, resilient, or as having Alzheimer’s dementia.
The regulons fall into three states. Interferon programs erode early. NF-κB suppression through BCL6 separates resilient people from those with dementia. A FLI1/IKZF1 network then expands and drives vascular-immune remodeling. The results replicate in independent cohorts.