Midlife Brain Immune Cells Swap, Potentially Linking Aging to Dementia

Scientists found that around age 50 the hippocampus loses its long-standing immune cells and gains more inflammatory ones, a shift that may underlie age-related brain disorders.

A study supported by the National Institutes of Health examined hippocampal samples from 40 neurologically healthy donors ranging from 20 to 95 years old. Using single-cell sequencing, epigenomic profiling and three-dimensional genome mapping, the researchers discovered that microglia, the brain’s resident immune cells, gradually decline from about age 50 to 75 and are supplanted by cells with strong inflammatory signals and characteristics of peripheral-blood immune cells.

This finding overturns the long-standing belief that microglia are embryonically derived and persist unchanged throughout life. The investigation also identified age-related deterioration in cells that uphold the blood-brain barrier and coordinated alterations in genome architecture across many brain cell types. investigators, including Richard Hodes, Nathan Zemke, Bing Ren and Xiangmin Xu, argue that this midlife immune remodeling may set the stage for the chronic inflammation observed in Alzheimer’s disease and other neurodegenerative conditions.

They propose that deciphering this transition could lead to interventions that preserve cognitive function in older adults. The results were published in Science and Science Advances as part of the NIH 4D Nucleome program.