SARS-CoV-2 infection leads to Tau pathological signature in neurons

Di Primio, C.; Quaranta, P.; Mignanelli, M.; Siano, G.; Bimbati, M.; Piazza, C. R.; Spezia, P. G.; Perrera, P.; Basolo, F.; Poma, A. M.; Costa, M.; Pistello, M.; Cattaneo, A.

doi:10.1101/2023.05.17.541098

bioRxiv · 10.1101/2023.05.17.541098

SARS-CoV-2 infection leads to Tau pathological signature in neurons

Di Primio, C.·Quaranta, P.·Mignanelli, M.·Siano, G.·Bimbati, M.·Piazza, C. R.·Spezia, P. G.·Perrera, P.·Basolo, F.·Poma, A. M.·Costa, M.·Pistello, M.·Cattaneo, A.

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Abstract

BackgroundThe coronavirus disease 19 (COVID-19) has represented an issue for global health since its outbreak in March 2020. It is now evident that the SARS-CoV-2 infection results in a wide range of long-term neurological symptoms and is worryingly associated with the aggravation of Alzheimers disease. Little is known about the molecular basis of these manifestations. MethodsSeveral SARS-CoV-2 strain variants were used to infect SH-SY5Y neuroblastoma cells and K18-hACE C57BL/6J mice. The Tau phosphorylation profile and aggregation propensity upon infection were investigated using immunoblot and immunofluorescence on cellular extracts, subcellular fractions, and brain tissue. The viral proteins Spike, Nucleocapsid, and Membrane were overexpressed in SH-SY5Y cells and the direct effect on Tau phosphorylation was checked using immunoblot experiments. ResultsUpon infection, Tau is phosphorylated at several pathological epitopes associated with Alzheimers disease and other tauopathies. Moreover, this event increases Taus propensity to form insoluble aggregates and alters its subcellular localization. ConclusionsOur data support the evidence that SARS-CoV-2 infection in the Central Nervous System triggers downstream effects altering Tau function, eventually leading to the impairment of neuronal function.

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Di Primio, C., Quaranta, P., Mignanelli, M., Siano, G., Bimbati, M., Piazza, C. R., Spezia, P. G., Perrera, P., Basolo, F., Poma, A. M., Costa, M., Pistello, M., Cattaneo, A.. 2023-05-17. SARS-CoV-2 infection leads to Tau pathological signature in neurons. https://doi.org/10.1101/2023.05.17.541098

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