Targeting SPI1 to mitigate amyloid-β pathology in Alzheimer's disease.

Abstract

SPI1, a transcription factor implicated in myeloid cell development, has emerged as a genetic risk factor for Alzheimer's disease (AD). Recent in vivo studies reveal that Spi1 knockdown in mice exacerbates AD pathology by increasing amyloid-β aggregation and gliosis while Spi1 overexpression ameliorates these features. Transcriptomic analyses suggest that Spi1 regulates microglial immune response, complement activation, and phagocytosis. SPI1 regulation of these processes may explain how SPI1 affects AD risk. Further studies, including human validation, are needed to explore the dynamic influence of SPI1 across AD stages, its applicability to clinical settings, and its potential as a therapeutic target.