In this section

Dr Kevin Moffat and Professor Bruno Frenguelli, University of Warwick

Drosophila as a model for Alzheimer's Disease

Abstract of research

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder characterised by the accumulation of extracellular beta-amyloid plaques and intracellular neurofibrillary tangles (NFT). The core constituent of NFTs is the Tau protein and molecular modifications in Tau result in the formation of the pathogenic NFTs. Accordingly, there has been great interest in these modifications and how they lead to the aggregation of Tau as a target for therapeutic intervention. Many transgenic mouse models have been generated to study AD and other Tau pathologies. As AD is a progressive condition it is often necessary to follow rodents for extended periods until some form of debilitation (cognitive, motor, and sensory) is evident. This has obvious welfare implications and is compounded by the difficulty in generating animal models that mimic all aspects of the human disease.

This project will use the invertebrate Drosophila melanogaster, or fruit fly, as a model in AD research. Previous research has shown human genes can be inserted into the fly genome and expressed, as a way of investigating the biochemical pathways that lead to the accumulation of Tau and the damage this causes. Along with modelling the basic neurobiology of AD and other Tau pathologies, this system will be used as a screen for drugs targeting the molecular modifications that lead to NFTs.

This work provides a way to rapidly explore novel pathways relevant to human brain disorders and allows high throughput screen for drugs influencing Tau-dependent pathology. This removes the need for mice in exploratory assays and speculative drug testing and could lead to improved animal models in AD research, resulting in both immediate and long term reductions in animal use.