Rxivist logo

A genome-wide survival analysis of 14,406 Alzheimer's disease (AD) cases and 25,849 controls identified eight previously reported AD risk loci and fourteen novel loci associated with age at onset. LD score regression of 220 cell types implicated regulation of myeloid gene expression in AD risk. In particular, the minor allele of rs1057233 (G), within the previously reported CELFI AD risk locus, showed association with delayed AD onset and lower expression of SPI1 in monocytes and macrophages. SPI1 encodes PU.1, a transcription factor critical for myeloid cell?development and function. AD heritability is enriched within the PU.1 cistrome, implicating a myeloid PU.1 target gene network in AD. Finally, experimentally altered PU.1 levels affect the expression of mouse orthologs of many AD risk genes and the phagocytic activity of mouse microglial cells. Our results suggest that lower SPI1 expression reduces AD risk by regulating myeloid gene expression and cell function.

Download data

  • Downloaded 1,644 times
  • Download rankings, all-time:
    • Site-wide: 4,050 out of 76,820
    • In neuroscience: 630 out of 13,769
  • Year to date:
    • Site-wide: 22,642 out of 76,820
  • Since beginning of last month:
    • Site-wide: 19,446 out of 76,820

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


PanLingua

Sign up for the Rxivist weekly newsletter! (Click here for more details.)


News