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

Summary

Together, these data suggest that mutations in PSEN1 enhance cytokine signalling via impaired regulated intramembrane proteolysis, thereby predisposing astrocytic inflammatory profiles. These findings support a two-hit contribution of PSEN1 mutations to fAD pathogenesis, not only impacting APP and Aβ processing but also altering the cellular response to inflammation. © 2025. The Author(s).

Authors Ziff OJ, Parfitt GM, Jolly S, Casey JM, Granat L, Samra S, Setó-Salvia N, Alatza A, Phadke L, Galet B, Ravassard P, Potier MC, Hardy J, Salih DA, Whiting P, Ducotterd F, Patani R, Wray S, Arber C
Journal Molecular neurodegeneration
Publication Date 2025 Jun 20;20(1):73
PubMed 40542358
PubMed Central PMC12181884
DOI 10.1186/s13024-025-00864-7

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