Mutations in PSEN1 predispose inflammation in an astrocyte model of familial Alzheimer's disease through disrupted regulated intramembrane proteolysis.

ABSTRACT:

Background

Mutations in PSEN1 cause familial Alzheimer's disease with almost complete penetrance. Age at onset is highly variable between different PSEN1 mutations and even within families with the same mutation. Current research into late onset Alzheimer's disease implicates inflammation in both disease onset and progression. PSEN1 is the catalytic subunit of γ-secretase, responsible for regulated intramembrane proteolysis of numerous substrates that include cytokine receptors. For this reason, we tested the hypothesis that mutations in PSEN1 impact inflammatory responses in astrocytes, thereby contributing to disease progression.

Methods

We developed patient-derived models of iPSC-astrocytes, representing three lines harbouring PSEN1 mutations and six control lines (includ

SUBMITTER: Ziff OJ 

PROVIDER: S-EPMC12181884 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature