Inhibition of high-fat diet-induced miRNA ameliorates tau toxicity in Drosophila

Alzheimer's disease (AD), caused by amyloid beta (Aβ) plaques and Tau tangles, is a neurodegenerative disease characterized by progressive memory impairment and cognitive dysfunction. High-fat diet (HFD), which induces type 2 diabetes, exacerbates Aβ plaque deposition in the brain. To investigate the function of HFD in Tau-mediated AD, we fed an HFD to the Drosophila Tau model and found that HFD aggravates Tau-induced neurological phenotypes. Since microRNAs (miRNAs) are biomarkers for diabetes and AD, we evaluated the expression levels of common miRNAs of HFD and AD in HFD-fed Tau model fly brains. Among the common miRNAs, the expression levels of Let-7 and miR-34 were increased. We found that the inhibition of these miRNAs alleviates Tau-mediated AD phenotypes. Our research provides valuable insights into how HFD accelerates tau toxicity. Additionally, our work highlights the therapeutic potential of targeting Let-7 and miR-34 to develop innovative treatment approaches for AD.