Cisternas, PabloTaylor, XavierMartinez, PabloMaldonado, OrlandoJury, NurLasagna-Reeves, Cristian A.2023-09-072023-09-072022-09-19Cisternas P, Taylor X, Martinez P, Maldonado O, Jury N, Lasagna-Reeves CA. The reduction of astrocytic tau prevents amyloid-β-induced synaptotoxicity. Brain Commun. 2022;4(5):fcac235. Published 2022 Sep 19. doi:10.1093/braincomms/fcac235https://hdl.handle.net/1805/35451Alzheimer’s disease is a neurological disorder characterized by the overproduction and aggregation of amyloid-beta and the phosphorylation and intraneuronal accumulation of tau. These events promote synaptic dysfunction and loss, leading to neurodegeneration and cognitive deficits. Astrocytes are intimately associated with synapses and become activated under pathological conditions, becoming neurotoxic and detrimentally affecting synapses. Although it has been established that reducing neuronal tau expression prevents amyloid-beta-induced toxicity, the role of astrocytic tau in this setting remains understudied. Herein, we performed a series of astrocytic and neuronal primary cultures to evaluate the effects of decreasing astrocytic tau levels on astrocyte-mediated amyloid-beta-induced synaptic degeneration. Our results suggest that the downregulation of tau in astrocytes mitigates the loss of synapses triggered by their exposure to amyloid-beta. Additionally, the absence of tau from astrocytes promotes the upregulation of several synaptoprotective genes, followed by increased production of the neuroprotective factor Pentraxin 3. These results expand our understanding of the contribution of astrocytic tau to the neurodegenerative process induced by amyloid-beta-stimulation and how reducing astrocytic tau could improve astrocyte function by stimulating the expression of synaptoprotective factors. Reducing endogenous astrocytic tau expression could be a potential strategy to prevent synaptic damage in Alzheimer's disease and other neurological conditions.en-USAttribution 4.0 InternationalTauAstrocytesSynaptotoxicityNeuroprotectionBeta-amyloidThe reduction of astrocytic tau prevents amyloid-β-induced synaptotoxicityArticle