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- W4313365573 abstract "Abstract Tauopathies, including Alzheimer’s disease (AD), are neurodegenerative diseases characterized by the accumulation of tau protein encoded by the MAPT (Microtubule Associated Protein Tau) gene. Various strategies targeting mechanisms to reduce tau pathology have been proposed and several tau-directed therapies are being investigated in clinical trials. Our lab previously developed a novel strategy to lower tau protein levels using antisense oligonucleotides (ASOs), showing that human tau (hTau) reduction in aged PS19 tauopathy mice reversed phosphorylated tau pathology, spared neurons, and prolonged survival. Currently, the tau-lowering ASO is being evaluated in the clinical trials with successful phase 1b results. Similarly, preclinical and clinical studies have demonstrated the use of other ASOs as effective therapeutic strategies. Acquiring ASOs for research purposes may be limited by partnerships with pharmaceutical companies. However, ASOs can be obtained through commercial vendors. The current study evaluates the efficacy of mouse and human tau-targeting ASOs obtained from a commercial vendor in various mouse models. We show that mice treated with purchased ASOs distribute among various brain cell types including neurons, microglia, and astrocytes. Mice treated with tau lowering ASOs show decreased mouse or human tau mRNA and protein levels. In addition, human tau lowering ASO-treated PS19 mice showed decreased phosphorylated tau (AT8) and gliosis relative to saline-treated PS19 mice. The results obtained in PS19 mice are consistent with data obtained from our previous study using a non-commercial tau-lowering ASO. Overall, the present study demonstrates the efficacy of commercially-available tau targeting ASOs in vivo to support their broad use by researchers." @default.
- W4313365573 created "2023-01-06" @default.
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- W4313365573 date "2022-12-29" @default.
- W4313365573 modified "2023-09-26" @default.
- W4313365573 title "Evaluating the efficacy of commercially available antisense oligonucleotides to reduce mouse and human tau<i>in vivo</i>" @default.
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- W4313365573 doi "https://doi.org/10.1101/2022.12.29.522258" @default.
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