Around the age of 50, the brain’s memory center begins replacing its established immune cells with more inflammatory ones. This discovery could explain how normal aging facilitates the onset of dementia, particularly Alzheimer’s disease.
Dr. Furhan Qureshi, a board-certified internal medicine physician, shared his surprise with Newsweek. He recalled, “In medical school, we learned that the brain’s primary immune cells present before birth remain throughout life, renewing within the brain.” However, the study indicates that around age 50, the hippocampus swaps these cells for more inflammatory ones, possibly from the blood. Qureshi added, “This changes our understanding of the origins of Alzheimer’s and similar diseases.” He stated that inflammation is commonly observed in Alzheimer’s patients, and this study suggests that it might be part of the normal aging process.
What the Study Found
Funded by the National Institutes of Health, the research focused on the hippocampus, the brain region vital for learning and memory. Scientists from the University of California, San Diego, the New York Genome Center, and the University of California, Irvine, examined postmortem hippocampal tissue from 40 neurologically healthy adults aged 20 to 95 using advanced single-cell techniques.
They discovered that the brain’s primary immune cells, microglia, decline between ages 50 and 75. As these cells disappear, they are replaced by more inflammatory cells similar to monocytes, immune cells typically found in the blood. This finding challenges the previous belief that microglia form in embryonic development and remain in the brain for life, self-renewing rather than being replaced.
Utilizing both standard gene-activity measurements and newer tools that map the genome’s three-dimensional structure and chemical modifications, researchers revealed changes in cell identity and origin unnoticed by gene activity alone. The study also identified early signs of deterioration in cells maintaining the blood-brain barrier, the protective boundary overseeing what enters the brain from the bloodstream.
What This Means for You
Aging remains the most significant risk factor for neurodegenerative diseases, with the hippocampus being particularly susceptible. Researchers estimate that 42% of Americans over the age of 55 will develop some form of dementia.
Although prior studies connected aging with increased inflammatory gene activity, they provided an incomplete picture of the decline’s causes. Ankit Chawla, a physician specializing in longevity and functional medicine, noted, “From a longevity viewpoint, the immune system is essential in aging processes, especially in the brain.” He affirmed that the study aligns with observations in his field.
Additionally, aging affects the genome’s 3D organization within brain cells, resulting in loss of astrocytes. These key cells support brain signaling and metabolism.
Newsweek contacted the study’s authors for additional insight.
Reference: Zemke, N. R., et al. (2026). Epigenetic and 3D genome reprogramming during the aging of the human hippocampus. Science. https://doi.org/10.1126/science.adt8307.
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