Patient-derived induced pluripotent stem cells with a C9orf72 expansion as a model to study frontotemporal dementia pathologies.

ABSTRACT: The neurodegenerative disorder frontotemporal dementia (FTD) can be caused by a repeat expansion (GGGGCC; G4C2) in C9orf72. The function of wild-type C9orf72 and the mechanism by which the C9orf72-G4C2 expansion causes FTD, however, remain unresolved. Diverse disease models, including human brain samples and differentiated neurons from patient-derived induced pluripotent stem cells (iPSCs), identified some hallmarks associated with FTD, but these models have limitations, including biopsies capturing only a static snapshot of dynamic processes and differentiated neurons being labor-intensive, costly, and postmitotic. We find that patient-derived iPSCs, without being differentiated into neurons, exhibit established FTD hallmarks, including increased lysosome pH, decreased lysosomal cathepsin

SUBMITTER: Infante-Tadeo S 

PROVIDER: S-EPMC12636529 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature