Using Drosophila amyloid toxicity models to study Alzheimer's disease

Alzheimer's disease (AD) is the most prevalent form of dementia and is characterised by a progressive loss of neurons, which manifests as gradual memory decline, followed by cognitive loss. Despite the significant progress in identifying novel biomarkers and understanding the prodromal pathology and symptomatology, AD remains a significant unmet clinical need. Lecanemab and aducanumab, the only Food and Drug Administration approved drugs to exhibit some disease-modifying clinical efficacy, target Aβ amyloid, underscoring the importance of this protein in disease aetiology. Nevertheless, in the absence of a definitive cure, the utilisation of preclinical models remains imperative for the identification of novel therapeutic targets and the evaluation of potential therapeutic agents. Drosophila melanogaster is a model system that can be used as a research tool to investigate neurodegeneration and therapeutic interventions. The short lifespan, low price and ease of husbandry/rearing make Drosophila an advantageous model organism from a practical perspective. However, it is the highly conserved genome and similarity of Drosophila and human neurobiology which make flies a powerful tool to investigate neurodegenerative mechanisms. In addition, the ease of transgenic modifications allows for early proof of principle studies for future therapeutic approaches in neurodegenerative research. This mini review will specifically focus on utilising Drosophila as an in vivo model of amyloid toxicity in AD.