INPP5D limits plaque formation and glial reactivity in the APP/PS1 mouse model of Alzheimer's disease

Abstract

The dual specificity lipid/protein phosphatase SHIP1 (encoded by the INPP5D gene) is enriched in myeloid cells. Single nucleotide polymorphisms (SNPs) in INPP5D coding and non-coding regions impact risk for developing late onset sporadic Alzheimers disease (LOAD). We present pathological analyses with spatial transcriptomics of mice with tamoxifen-sensitive microglial knockdown of Inpp5d and show exacerbated plaque pathology, plaque-associated microglial density, and altered gene expression around plaques, suggesting novel markers for plaque-associated reactive microglia.