Astrocytic accumulation of tau fibrils isolated from Alzheimer's disease brains induces inflammation, cell-to-cell propagation and neuronal impairment.

ABSTRACT: Accumulating evidence highlights the involvement of astrocytes in Alzheimer's disease (AD) progression. We have previously demonstrated that human iPSC-derived astrocytes ingest and modify synthetic tau fibrils in a way that enhances their seeding efficiency. However, synthetic tau fibrils differ significantly from in vivo formed fibrils. To mimic the situation in the brain, we here analyzed astrocytes' processing of human brain-derived tau fibrils and its consequences for cellular physiology. Tau fibrils were extracted from both AD and control brains, aiming to examine any potential differences in astrocyte response depending on the origin of fibrils. Our results show that human astrocytes internalize, but fail to degrade, both AD and control tau fibrils. Instead, pathogenic, seeding capa

SUBMITTER: Eltom K 

PROVIDER: S-EPMC10898102 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature