AlzheimersInAction: A multi-disciplinary approach to determine the cellular and molecular mechanisms underlying the inflammatory response to amyloid-β in Alzheimer’s disease.

ended

In addition to devastation for the patients and their families, Alzheimer’s disease (AD) generates enormous costs for the wider European economy and is an urgent health priority. There are currently no drug treatments that can cure AD or other common forms of dementia. This absence of therapeutic interventions comes from a lack of understanding about the biological changes that cause most neurological diseases. It is critical to fill in the gaps in our understanding of what biological changes are occurring during the early stages of AD in order to develop treatments that could slow progression or delay the onset of AD. The comorbid nature of this disease and the difficulty of capturing neurobiological processes in action in real time have made it very difficult to determine what changes in the AD brain actually cause the synaptic and neuronal damage that leads to behavioural symptoms. To overcome these difficulties, I propose a multi-disciplinary approach that combines and develops cutting-edge techniques in Drosophila cell biology, molecular biology, time-lapse imaging, computational modelling, and electrophysiology in parallel with exploitation of the powerful molecular genetics, versatile promoter systems and rapid development of flies. Specifically, throughout AlzheimersInAction I will use these techniques to develop an in depth understanding of how an overproduction of amyloid-β causes downstream pathologies, and how activation of the immune cells during AD causes disease pathogenesis. By the completion of this project we will have a greater understanding of the cellular and molecular mechanisms underlying the inflammatory response to Aβ in Alzheimer’s disease. With 10.5 million EU citizens currently living with dementia, and this value predicted to increase at an alarming rate of 2-fold every 20 years, the outputs from AlzheimersInAction will contribute to the research output, visibility, and economy of Europe.