Knockout of TSPO delays and reduces amyloid, Tau, astrocytosis and behavioral dysfunctions in Alzheimer’s disease

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dc.contributor.authorCeyzériat, Ken_AU
dc.contributor.authorMeyer, Len_AU
dc.contributor.authorBoutjelda, Fen_AU
dc.contributor.authorTsartsalis, Sen_AU
dc.contributor.authorAmossé, Qen_AU
dc.contributor.authorMiddleton, RJen_AU
dc.contributor.authorLiu, GJen_AU
dc.contributor.authorBanati, RBen_AU
dc.contributor.authorZilli, Ten_AU
dc.contributor.authorGaribotto, Ven_AU
dc.contributor.authorMillet, Pen_AU
dc.contributor.authorTournier, BBen_AU
dc.date.accessioned2022-08-19T05:53:35Zen_AU
dc.date.available2022-08-19T05:53:35Zen_AU
dc.date.issued2022-03-28en_AU
dc.date.statistics2022-08-01en_AU
dc.descriptionThis article is a preprint and has not been certified by peer review.en_AU
dc.description.abstractThe 18kDa translocator protein (TSPO) is up-regulated in glial cells in neurodegenerative diseases. In Alzheimer’s disease (AD) animal models, TSPO is first overexpressed in astrocytes and then in microglia. However, the precise role of TSPO in the onset and progression of pathology and symptoms characteristic of the disease remains unknown. Here, we report that in the absence of TSPO in 3xTgAD mice the expected disease onset is significantly delayed and a reduction is seen in the hippocampal load of poorly and highly aggregated forms of Tau (−44% and −82%, respectively) and Aβ42 (−25% and −95%, respectively), at 9 months of age. In addition, the astrocyte reactivity was decreased in 3xTgAD.TSPO−/− mice with a reduction in the morphologic complexity and the size of astrocytes in the dorso-dorsal hippocampus and the hilus. Functionally, the absence of TSPO ameliorated the cognitive consequences of adeno-associated virus-induced Tau over-expression in the hippocampus. This suggests that TSPO plays an important role in the active disease progression of AD. TSPO-inhibiting drugs thus merit further exploration as to their potential to reduce the rate of neurodegenerative disease progression. © 2022 The Authorsen_AU
dc.description.sponsorshipA part of this work was supported by the Velux foundation (grant number 1123).en_AU
dc.identifier.articlenumber2022.2003.2026.485919en_AU
dc.identifier.citationCeyzériat, K., Meyer, L., Bouteldja, F., Tsartsalis, S., Amossé, Q., Middleton, R. J., Liu, G. J., Banati, R. B., Zilli, T., Garibotto, V., Millet, P. & Tournier, B. B. (2022). Knockout of TSPO delays and reduces amyloid, Tau, astrocytosis and behavioral dysfunctions in Alzheimer's disease. bioRxiv, preprint. doi:10.1101/2022.03.26.485919en_AU
dc.identifier.issn2692-8205en_AU
dc.identifier.journaltitlebioRxiven_AU
dc.identifier.urihttps://doi.org/10.1101/2022.03.26.485919en_AU
dc.identifier.urihttps://apo.ansto.gov.au/dspace/handle/10238/13586en_AU
dc.language.isoenen_AU
dc.publisherCold Spring Harbor Laboratoryen_AU
dc.subjectSymptomsen_AU
dc.subjectBrainen_AU
dc.subjectHippocampusen_AU
dc.subjectProteinsen_AU
dc.subjectAstrocytomasen_AU
dc.subjectNeurologyen_AU
dc.titleKnockout of TSPO delays and reduces amyloid, Tau, astrocytosis and behavioral dysfunctions in Alzheimer’s diseaseen_AU
dc.typeJournal Articleen_AU
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