Palikaras, Konstantinos et al. (2021) International Worm Meeting "Mitochondrial defects manifest an early pathogenic event undermining organismal fitness in a Tauopathy model"

Akbari, Mansour, Achanta, Kavya, Bohr, Vilhelm, Palikaras, Konstantinos

[International Worm Meeting, 2021]

Battling age-associated neurodegenerative pathologies and their pervasive societal impact, is a global enterprise. Alzheimer's disease (AD) is the most common dementia affecting elderly population and there is not any efficient therapeutic strategy until now. Age-dependent impairment of mitochondrial homeostasis is a common feature in evolutionary divergent organisms and is associated with neuronal loss and cognitive decline in AD. However, whether mitochondrial dysfunction is a culprit or bystander of AD pathology remain still elusive. Here, we utilized transgenic nematodes expressing the full length of wild type Tau (Tauwt-lo) in neuronal cells and monitored several aspects of mitochondrial morphology. Although Tauwt-lo expressing nematodes do not present Tau aggregates during larval stages, they display increased mitochondrial damaged and locomotion defects. Interestingly, calcium chelating agents restores mitochondrial activity and motility in Tauwt-lo expressing larvae suggesting that cytoplasmic calcium elevation mediates neuronal impairment. Our findings in their totality suggest that mitochondrial damage is an early pathogenic event of AD that is taking place before Tau aggregation undermining neuronal homeostasis and organismal fitness during aging.