Midlife brain shift replaces protective cells with inflammatory ones, raising dementia risk

Analysis of postmortem hippocampal samples from 40 neurologically normal donors spanning ages 20 to 95 showed that the brain’s native immune cells, microglia, begin to be supplanted by inflammatory cells arriving from the blood once individuals reach roughly age 50. While microglia normally clear debris and protect neural tissue, the incoming cells carry heightened inflammatory signals, a shift the authors suggest may underlie the rise in neuroinflammation and neurodegenerative disorders like dementia.

The study also documented deterioration of the blood-brain barrier and extensive changes in DNA methylation and gene expression across the sampled brains. The researchers highlighted that blood-derived cells are more accessible, raising the prospect of modifying them to become less harmful as a new therapeutic avenue for Alzheimer’s and related conditions. Limitations include the small, cross-sectional sample and focus on the hippocampus alone, which may not represent the whole brain. The work was funded by the National Institutes of Health and published in Science.