[
International Worm Meeting,
2019]
Background: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by two hallmarks: extracellular plaques composed of amyloid-? (A?) deposits and intraneuronal accumulation of hyper- and abnormal phosphorylated tau, also called neurofibrillary tangles (NFT). Despite an important number of studies, the nature of Tau species toxicity -aggregated insoluble Tau and/or oligomeric soluble hyperphosphorylated Tau - remain ill understood. Objectives: Our research project aims to characterize which state of Tau phosphorylation contributes the more to neuronal toxicity and identify the underlying mechanisms. Methods: To assess these objectives, we have generated transgenic C. elegans models expressing either a human hyperphosphorylated tau (incorporation of 12 glutamate to mimic Tau hyperphosphorylation found in AD's patients) or human wild type Tau in the GABAergic motoneurons. Then, we have measured their behaviour (worm motility, length, percentage of immobility in solid and liquid medium) using WormLab software. We have also characterized the neurodegeneration induced by Tau phosphorylation. Results: At day 1 until day 13, we have measured that strain with hyperphosphorylated Tau have a significant decrease of their swimming speed compared to the wild type tau strain and N2 control . The percentage of immobile worms is higher for hyperphosphorylated tau at day 1 (24%) compared to the control (3%) and wild type tau (1%). Moreover, the induction of a heat stress by placing worms at 37 degrees for 15 minutes worsen significantly the mobility in the only hyperphosphorylated tau strain at day 1 and until day 13 compared to control. Finally, the percentage of immobility is higher in the hyperphosphorylated species (36-53%) than in the wild type tau (2%) and control (1.7%) at day 1, suggesting heat sensitivity for the hyperphosphorylated model. Conclusion: All together, our results reveal that hyperphosphorylated models drastically impair C. elegans motility in an early stage of life, suggesting that phosphorylation plays a detrimental role in neurodegeneration. An update of our findings will be presented.