Intraneuronal tau aggregation induces the integrated stress response in astrocytes.

ABSTRACT: Progressive aggregation of tau protein in neurons is associated with neurodegeneration in tauopathies. Cell non-autonomous disease mechanisms in astrocytes may be important drivers of the disease process but remain largely elusive. Here, we studied cell type-specific responses to intraneuronal tau aggregation prior to neurodegeneration. To this end, we developed a fully human co-culture model of seed-independent intraneuronal tau pathology, which shows no neuron and synapse loss. Using high-content microscopy, we show that intraneuronal tau aggregation induces oxidative stress accompanied by activation of the integrated stress response specifically in astrocytes. This requires the direct co-culture with neurons and is not related to neurodegeneration or extracellular tau levels. Tau-direct

SUBMITTER: Batenburg KL 

PROVIDER: S-EPMC10080549 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature