Age-Related Changes in the Brain’s Immune Cells and Implications for Dementia

A recent study has revealed that around the age of 50, the brain begins replacing its traditional immune cells with more inflammatory ones. This shift might explain why normal aging contributes to diseases like Alzheimer’s. Furhan Qureshi, a board-certified internal medicine physician, highlighted the significance of these findings. “During my medical training, I learned that the brain’s main immune cells, microglia, stay with us for life,” Qureshi told Newsweek. “This research suggests that around midlife, the hippocampus begins exchanging these cells for more inflammatory ones, possibly from the bloodstream, which is a significant change to our understanding.”

Qureshi emphasized that this discovery could change scientists’ views on dementia, particularly Alzheimer’s. “It’s been known that Alzheimer’s brains show inflammation,” he explained. “This study suggests that this inflammation might be a normal part of aging, starting decades before symptoms appear.” The study indicates that the brain’s immune landscape undergoes silent changes over many years.

What the Study Found

The research, supported by the National Institutes of Health, focused on the hippocampus, a key region for learning and memory. Collaborating institutions included the University of California, San Diego, the New York Genome Center, and the University of California, Irvine. Researchers examined hippocampal tissue from 40 neurologically healthy adults aged 20 to 95, using advanced single-cell techniques.

They found that microglia decline steadily between ages 50 and 75. As microglia diminish, they are replaced by cells exhibiting stronger inflammatory traits and characteristics of monocytes, which are typically found in the bloodstream. This discovery challenges the belief that microglia originate during embryonic development and remain in the brain indefinitely.

The researchers identified this shift by combining standard gene activity analysis with modern tools mapping the genome’s 3D structure and its chemical modifications, the epigenome. These combined approaches revealed cell identity and origin changes that might go undetected through gene activity alone. Additionally, early signs of decline appeared in the cells maintaining the blood-brain barrier, the protective border regulating the bloodstream’s access to the brain.

What This Means for You

Aging is the strongest risk factor for neurodegenerative diseases, with the hippocampus being particularly susceptible. Researchers estimated that about 42% of Americans over age 55 will develop some form of dementia.

Previous studies connected aging to increased inflammatory gene activity, but gene expression alone did not capture the complete picture of the decline’s causes. Ankit Chawla, a longevity and functional medicine physician, noted that the findings align with his field’s observations. “From a longevity viewpoint, the immune system plays a crucial role in aging processes, particularly within the brain,” Chawla shared with Newsweek. “It’s no surprise this study highlights its significance in the aging brain.”

The study also discovered that aging reduces the genome’s 3D organization across brain cell types, along with significant loss of astrocytes, which are essential for supporting brain signaling and metabolism.

Newsweek has reached out to the study’s authors for further details. The reference for this study is: 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.