Study finds cancer-associated somatic mutations in brain immune cells linked to Alzheimer's neuroinflammation
By
August Yue Huang1,2,3,22 Send email to [email protected]
Summary
This study investigates the link between Alzheimer's disease (AD) and somatic mutations in brain immune cells. Deep sequencing of 311 brain samples revealed enrichment of somatic single-nucleotide variants (sSNVs) in cancer driver genes—particularly those associated with clonal hematopoiesis (CH)—in AD brains. These mutations were found in 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 further indicated that these variants drive inflammatory and proliferative states in microglia, potentially contributing to neuroinflammation and neurodegeneration in Alzheimer's disease progression.
Source
bskyStudy finds cancer-associated somatic mutations in brain immune cells linked to Alzheimer's neuroinflammationcell.comKey quotes
· 3 pulledDeep (>1,000×) panel sequencing of 311 brain samples revealed enrichment of somatic single-nucleotide variants (sSNVs) in cancer driver genes 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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