Inpp5d haplodeficiency alleviates tau pathology in the PS19 mouse model of Tauopathy.

ABSTRACT:

Introduction

A noncoding variant (rs35349669) within INPP5D, a lipid and protein phosphatase restricted to microglia in the brain, is linked to increased susceptibility to Alzheimer's disease (AD). While Inpp5d is well-studied in amyloid pathology, its role in tau pathology remains unclear.

Methods

PS19 Tauopathy mice were crossed with Inpp5d-haplodeficient (Inpp5d+/-) mice to examine the impact of Inpp5d in tau pathology.

Results

Increased INPP5D expression correlated positively with phospho-Tau AT8 in PS19 mice. Inpp5d haplodeficiency mitigated hyperphosphorylated tau levels (AT8, AT180, AT100, and PHF1) and motor deficits in PS19 mice. Transcriptomic analysis revealed an up-regulation of genes associated with immune response and cell migration.

Discussion

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SUBMITTER: Soni DM 

PROVIDER: S-EPMC11247686 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature