The Alzheimer's disease risk factor INPP5D restricts neuroprotective microglial responses in amyloid beta-mediated pathology.

ABSTRACT:

Introduction

Mutations in INPP5D, which encodes for the SH2-domain-containing inositol phosphatase SHIP-1, have recently been linked to an increased risk of developing late-onset Alzheimer's disease. While INPP5D expression is almost exclusively restricted to microglia in the brain, little is known regarding how SHIP-1 affects neurobiology or neurodegenerative disease pathogenesis.

Methods

We generated and investigated 5xFAD Inpp5d^fl/fl Cx3cr1^Ert2Cre mice to ascertain the function of microglial SHIP-1 signaling in response to amyloid beta (Aβ)-mediated pathology.

Results

SHIP-1 deletion in microglia led to substantially enhanced recruitment of microglia to Aβ plaques, altered microglial gene expression, and marked improvements in neuronal health.

SUBMITTER: Samuels JD 

PROVIDER: S-EPMC10576836 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature