Investigating a new tau aggregation inhibitor “RE01” in PS19 transgenic mice

Alzheimer’s disease (AD), which is characterized by extracellular accumulation of amyloid-beta peptide and intracellular aggregation of hyperphosphorylated tau, is the most common form of dementia. During AD pathogenesis, tau is abnormally phosphorylated and aggregating within neurons. As a result of continuous intraneuronal tau aggregation, neurofibrillary tangles are formed. The aim of our project is to determine, whether inhibiting tau protein aggregation with a novel anti-aggregative compound “RE01” improves survival, behavior and neuropathology in a tau-transgenic mouse model. RE01 is an FDA-approved anti-cancer drug, that we intend to use for drug repurposing. We administered RE01 via the chow at concentrations of 25 mg/kg and 50 mg/kg, in PS19 mice. Treatment started after weaning at 3-4 weeks of age. Behavior experiments were carried out at 8-10 months of age testing cognition, spatial memory and motor function.Our results indicate gender-specific effects. Notably, 25mg/kg treated male mice exhibited a significant improvement in motor functions compared to vehicle-treated mice. These experiments will pave the way for the development of new anti-aggregative compounds against tau. These may be valuable for the treatment of tauopathies like AD in the future.