Immune cells from the blood protect the brain during aging

A key role in the work was played by an interdisciplinary methodology that combined molecular biology, genetics, and computational approaches. The team used a unique opportunity to compare blood samples and post‑mortem brain tissues collected at the Stanford Rapid Autopsy Center and in the Alzheimer’s disease sequencing project at the University of Washington. This material made it possible to directly compare immune cells in the bloodstream and in the brain in people with and without Alzheimer’s disease.

To determine the origin of immune cells in the brain, researchers used a method for tracking cell lineages based on somatic mutations. The fact is that as we age, random mutations accumulate in the stem cells of the bone marrow, and all descendants of these cells inherit the same set of changes. If the same mutations are found in both the blood and brain cells, this serves as reliable evidence that brain cells originate from precursors in the bloodstream, similar to how commercial ancestry tests identify common roots based on matching genetic markers.

The analysis showed that immune cells do indeed migrate from peripheral blood to the brain, and this process begins already in middle age. Moreover, once they enter the nervous tissue, these cells acquire the properties of specialized microglia, that is, they essentially re‑learn to perform the tasks of local immune defense. It is noteworthy that this mechanism appears to be characteristic specifically of humans: in mice and other primates, such large‑scale replacement of microglia by peripheral cells is not observed.

Previously, the group had already drawn attention to the link between certain clones of immune cells (arising during so‑called clonal hematopoiesis of undetermined potential) and a reduced risk of Alzheimer’s disease. New data have made it possible to explain this pattern. It is likely that the influx of such cells from the blood can influence the brain’s resistance to neurodegeneration. As Jaiswal notes, this means that the life history of blood stem cells can determine the risk of neurological diseases through changes in the composition and function of microglia.

The discovery has not only fundamental but also practical significance. Now that it is достоверно known that peripheral immune cells can penetrate the brain, new opportunities for developing immunotherapies are emerging. For example, one can imagine an approach in which immune cells are pre‑trained to break down amyloid and tau protein aggregates — key pathological structures in neurodegenerative diseases — and then are introduced to the patient as a preventive measure even before the active accumulation of these proteins begins.

Furthermore, the study opens up a new direction for studying risk factors, since any influences affecting hematopoiesis or the condition of the bone marrow could potentially alter the brain’s immune landscape and thereby influence the development of neurological disorders. According to the authors, what was particularly exciting in this work was the discovery of a unique feature of human aging that no one had suspected before.

The work of Stanford scientists not only corrects previous ideas about the brain’s closedness to the immune system but also offers a fundamentally new perspective on the mechanisms of protecting nervous tissue in old age. This could become the basis for innovative strategies for the prevention and treatment of neurodegenerative diseases, relying on the controlled migration and reprogramming of immune cells.