Cancer-associated somatic variants in microglia drive inflammation and proliferation in Alzheimer's disease
By
August Yue Huang1,2,3,22 Send email to [email protected]
Summary
This study investigates the link between somatic mutations and Alzheimer's disease (AD) by performing deep (>1,000×) panel sequencing on 311 brain samples. The researchers found enrichment of somatic single-nucleotide variants (sSNVs) in cancer driver genes in AD brains, particularly in genes associated with clonal hematopoiesis (CH). These variants were associated with clonal expansion and were carried by microglia-like brain macrophages (MLBMs) across multiple brain regions and in paired blood samples, suggesting a hematopoietic origin. Single-nucleus RNA sequencing data from 62 additional samples revealed that these cancer-associated somatic variants drive microglia toward inflammatory and proliferative states, potentially contributing to neuroinflammation and neurodegeneration in AD progression.
Source
bskyCancer-associated somatic variants in microglia drive inflammation and proliferation in Alzheimer's diseasecell.comKey quotes
· 3 pulledSomatic single-nucleotide variants (sSNVs) in cancer driver genes were enriched in AD brains, especially in genes associated with clonal hematopoiesis (CH).
These sSNVs were associated with clonal expansion and carried by both microglia-like brain macrophages (MLBMs) in multiple brain regions as well as paired blood, suggesting a likely hematopoietic origin.
Cancer-associated somatic variants are enriched in the brain immune cells of Alzheimer's disease (AD) patients, driving them toward inflammation and proliferation, which may contribute to neuroinflammation and neurodegeneration during AD progression.
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