Researchers rethink the aging brain’s immune system, immune cells from the body flow into the brain

Amazing stuff!

"Contrary to longstanding belief, immune cells from the rest of the body flow into the brain as it ages, a finding that could open new paths for treating neurodegenerative disease."

"In brief

• Stanford scientists discovered that immune cells in the blood travel into the central nervous system.
• The discovery upends conventional wisdom that the immune systems of the brain and the rest of the body are walled off from each other.
• The researchers built on recently developed genetics tools to trace the origins of immune cells in the brain.
• The discovery suggests researchers could one day engineer peripheral immune cells to travel to the brain to treat or prevent neurological diseases.

..."

From the abstract:

"Microglia are the resident macrophages of the central nervous system. In mice, microglia seed the brain during embryogenesis and can be maintained throughout life with minimal input from adult hematopoiesis.

The origins of human microglia are less clear, but recent evidence suggests that marrow-derived cells contribute to the human microglial pool in certain individuals.

Here, to investigate the ontogeny of human microglia, we develop an approach that uses the collection of accumulated somatic mutations which uniquely labels each clone of cells to track the infiltration of marrow-derived cells into the human brain.

Applying this approach to 20 aged individuals, we find evidence of an influx of marrow-derived cells into the brain in all examined individuals.

Single cell analysis, including single cell lineage tracing using mitochondrial DNA variants, demonstrates that these infiltrating cells are similar to microglia and can comprise a large fraction of the microglial pool.

Analysis of human cohort data demonstrates a protective association between most types of clonal hematopoiesis and Alzheimer’s disease.

In sum, this work uncovers a widespread influx of myeloid cells into the healthy human brain which contributes to the pool of human microglia and becomes common with aging."

Stanford Report

Researchers rethink the aging brain’s immune system | Stanford Report "A discovery from an unusual team of computer scientists and pathologists overturns longstanding dogma and could point the way toward new therapies for neurodegenerative disease."

Somatic mutations reveal the ontogeny of microglia in human aging (no public access)

Somatic mutations reveal the ontogeny of human microglia (preprint, open access)