Unique blood cells are linked to reduced Alzheimer’s disease risk

Clonal hematopoiesis of indeterminate potential (CHIP), a condition that changes the DNA of some blood cells and increases the risk for blood cancers and cardiovascular disease, may reduce a person’s risk of developing Alzheimer’s disease. This finding from an NIA-funded study published recently in Nature Medicine may provide new insights into the role that blood cells play in brain health.

Blood cells live short lives and must be continuously replaced. The process of producing new blood cells is called hematopoiesis and occurs in the bone marrow. As blood cells are depleted, a pool of cells in the bone marrow called hematopoietic stem cells (HSCs) multiply to replenish them. Normally, tens of thousands of HSCs grow up to be exact copies of the replaced blood cells. In CHIP, however, the genes of some hematopoietic stem cells change and produce slightly different blood cells.

People with CHIP can live for many years but have an increased risk for blood cancer and cardiovascular disease compared to people without CHIP. The condition is common in older adults, and researchers estimate that 10% to 30% of people over 70 years old have CHIP. While most research on this condition has focused on how it affects cardiovascular health, its effect on the brain is not yet well understood. To address this gap, a research team led by Stanford University scientists is exploring how CHIP influences Alzheimer’s risk in older adults.

In this study, the scientists analyzed blood samples from 1,362 people with Alzheimer’s and 4,368 people without the disease. Then they sequenced the DNA from the blood cells to determine who had CHIP. Remarkably, the researchers found that people with CHIP had a reduced risk of developing Alzheimer’s.

Next, the team sequenced the DNA from the microglia of the brains of eight people with CHIP. As the brain’s immune cells, microglia play a central role in brain function and health. In Alzheimer’s, microglia fail to perform their job, instead damaging neurons they are meant to protect. For seven of these individuals, the researchers found microglia in the brain that carried the same CHIP variant in the blood cells. While not conclusive, this suggests that some of these variant blood cells migrate to the brain and may support microglial function.

Overall, these findings suggest that CHIP may provide some protection from Alzheimer’s. Future studies will explore the differences between the brain’s immune cells that carry CHIP variants and those that do not. Understanding why CHIP is linked to reduced Alzheimer’s risk could uncover new insights into slowing the progression of the disease.

This research was supported in part by NIA grants AG053959, AG077443, AG066849, AG059727, and AG052409.

These activities relate to NIH’s AD+ADRD Research Implementation Milestone 1.A, “Enable precision medicine research by supporting deep and longitudinal molecular endophenotyping of existing and new at-risk cohorts as well cohorts and/or individuals who resist disease despite high genetic risk (e.g. Down Syndrome, ApoE 4 homozygous, FAD mutation carriers).”

Reference: Bouzid H, et al. Clonal hematopoiesis is associated with protection from Alzheimer’s disease. Nature Medicine. 2023. Epub June 15. doi: 10.1038/s41591-023-02397-2.

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