A study in Nature has challenged a long-standing assumption about the immune cells that live inside the human brain.
Microglia are macrophage-like immune cells that reside in the central nervous system. In mice, they enter the brain during embryonic development and can largely maintain themselves throughout life without substantial replacement from circulating blood cells.
The new human study found something more dynamic: in every older individual examined, researchers detected bone-marrow-derived cells that had entered the brain and adopted microglia-like identities.
How the researchers traced cell ancestry
The central problem is that a cell does not carry a label saying where it came from.
The researchers used somatic mutations as natural lineage markers. These are DNA changes acquired during a person's lifetime. Cells descended from the same ancestral cell can share characteristic mutations, allowing researchers to reconstruct family relationships between cell populations.
The team applied this approach to tissue from 20 older individuals and combined it with single-cell analysis, including lineage tracing using mitochondrial DNA variants.
What they found
The investigators found evidence of bone-marrow-derived cells entering the brain in all 20 individuals studied.
Some of these cells closely resembled microglia and, in some individuals, made up a substantial fraction of the microglial pool.
This suggests that human microglia are not necessarily an entirely closed population established before birth and maintained unchanged throughout life.
Why this is biologically important
Microglia help maintain brain tissue, remove cellular debris, respond to injury and participate in inflammatory processes.
If a meaningful proportion of these cells can be replaced by cells originating in bone marrow, then ageing of the immune system outside the brain may influence the cellular composition of the brain itself more directly than previously appreciated.
That could matter for research into neurodegeneration, inflammation and age-related changes in brain function.
What the study does not show
The study does not establish that incoming bone-marrow-derived cells cause cognitive decline, Alzheimer's disease or any other neurological condition.
It also examined older individuals, so it cannot by itself define how much replacement occurs at younger ages or precisely when infiltration accelerates.
The result is principally about cellular origin and turnover, not a treatment target.
Why human data matter here
Mouse studies are essential for mechanistic neuroscience, but immune-cell turnover can differ between species.
By tracing naturally occurring mutations in human tissue, the researchers were able to examine a question that is difficult to answer by extrapolating from animal models alone.
The next questions are whether the incoming cells behave differently from embryonically derived microglia, what drives their recruitment, and whether their proportion is associated with particular diseases or patterns of brain ageing.
Primary source
- Belk JA, et al. Somatic mutations reveal the ontogeny of microglia in human ageing. Nature. 2026. DOI: 10.1038/s41586-026-10939-0. https://www.nature.com/articles/s41586-026-10939-0