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Osteopontin drives neuroinflammation and cell loss in MAPT-N279K frontotemporal dementia patient neurons

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE230520 | GEO | 2024/04/15

REPOSITORIES: GEO

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Osteopontin drives neuroinflammation and cell loss in MAPT-N279K frontotemporal dementia patient neurons

Project description:Frontotemporal dementia (FTD) is an incurable group of early-onset dementias that can be caused by deposition of hyperphosphorylated tau in patient brains. However, the mechanisms leading to neurodegeneration remain largely unknown. Here, we combined single-cell analyses of FTD patient brains with a stem cell culture and transplantation model of FTD. We identified disease phenotypes in FTD neurons carrying the MAPT-N279K mutation, which were related to oxidative stress, oxidative phosphorylation and neuroinflammation with an upregulation of the inflammation-associated protein osteopontin (OPN). Human FTD neurons survived less and elicited an increased microglial response after transplantation into the mouse forebrain, that we further characterized by single nucleus RNA-sequencing of microdissected grafts. Notably, downregulation of OPN in engrafted FTD neurons resulted in improved engraftment and reduced microglial infiltration, indicating an immune-modulatory role of OPN in patient neurons, which may represent a potential therapeutic target in FTD.

2024-04-15 | GSE230519 | GEO

Osteopontin drives neuroinflammation and cell loss in MAPT-N279K frontotemporal dementia patient neurons

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Osteopontin drives neuroinflammation and cell loss in MAPT-N279K frontotemporal dementia patient neurons

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