New findings from researchers at the Mount Sinai School of Medicine in New York reveal that microglia, the brain’s resident immune cells, are governed by the SPI1 proto-oncogene. This discovery points to SPI1 as a potential new target for Alzheimer’s disease therapies. The study was published in Nature Genetics.
To reach their conclusions, the scientists analyzed brain tissue from 150 individuals, some with Alzheimer’s disease and some without. The samples were obtained through biopsy or autopsy. After isolating the microglia, the researchers decoded the DNA inside these cells. The resulting data highlighted a central role for SPI1 in regulating a broad network of genes involved in microglial function.
Modulating SPI1 activity appeared to shift the behavior of many other genes, effectively reshaping how microglia operate. The study details how these gene interactions drive microglial processes, linking SPI1 to the larger genetic program that governs brain immune activity. Historically, SPI1 has been described as a proto-oncogene, meaning that mutations in SPI1 can contribute to cancer in some contexts.
Microglia serve as the brain’s immune sentinels, yet their responsibilities extend far beyond infection defense. The brain is shielded from most systemic pathogens by the blood–brain barrier, but microglia participate in a wide range of brain functions. In recent years, mounting evidence has underscored microglia as central players in neurodegenerative diseases, including Alzheimer’s disease, where they influence inflammation, synapse remodeling, and neuronal health.
This study stands out as the largest and most comprehensive examination of microglia in human brain tissue to date. Isolating these cells in quantity is exceptionally challenging, making the work a significant advance toward mapping the genetic and molecular landscape of Alzheimer’s disease and identifying potential therapeutic strategies.