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Astrocytic uptake of neuronal corpses promotes cell-to-cell spreading of tau pathology
Acta Neuropathol Commun. 2023 Jun 17;11(1):97. doi: 10.1186/s40478-023-01589-8.
Tobias Mothes 1, Benjamin Portal 2, Evangelos Konstantinidis 1, Khalid Eltom 1, Sylwia Libard 3, Linn Streubel-Gallasch 1, Martin Ingelsson 1 4 5, Jinar Rostami 1, Maria Lindskog 2, Anna Erlandsson 6
Abstract:
...Here we demonstrate...that human astrocytes...promot(e) cell-to-cell spreading of pathological tau. Human astrocytes engulf and process, but fail to fully degrade dead neurons with tau pathology, as well as synthetic tau fibrils and tau aggregates isolated from AD brain tissue. Instead, the pathogenic tau is spread to nearby cells via secretion and tunneling nanotube mediated transfer. By performing co-culture experiments we could show that tau-containing astrocytes induce tau pathology in healthy human neurons directly. Furthermore, our results from a FRET based seeding assay, demonstrated that the tau proteoforms secreted by astrocytes have an exceptional seeding capacity, compared to the original tau species engulfed by the cells. Taken together, our study establishes a central role for astrocytes in mediating tau pathology, which could be of relevance for identifying novel treatment targets for AD and other tauopathies.
PMID: 37330529
Free Full-Text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10276914/
Tags: Alzheimer’s, astrocytes, cell culture, tau, Tau spreading