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

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

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, though recently there have been great progress with promising results in clinical trials with Lecanamab and Donanemab able to slow AD progression by 27% and 35% respectively. The absence of therapeutic interventions has come from a lack of understanding about the biological changes that cause most neurological diseases. It appears that we are now at a turning point in the fight against AD, and 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 improve upon the development of treatments so we can further slow progression or delay the onset of AD. To overcome the difficulties of co-morbidity and capturing processes in real time, we took a multi-disciplinary approach that combines and develops cutting-edge techniques in Drosophila cell biology, molecular biology, and time-lapse imaging, in parallel with exploitation of the powerful molecular genetics, versatile promoter systems and rapid development of flies. Our aim was to identify potential targets for therapeutic intervention that would slow or stop AD progression from the earliest stages. Throughout AlzheimersInAction, we developed an in-depth understanding of how an overproduction of amyloid-β (Aβ) causes downstream pathologies, and how activation of the immune cells during AD causes disease pathogenesis. Additionally, we undertook a large-scale compound screen which identified pathways that, when altered, could the overproduction of Aβ that occurs at the earliest stages of AD. In conclusion, our findings from AlzheimersInAction have have identified compounds and pathways that can be targeted to slow or even stop the overproduction of Aβ that occurs in early AD. With recent clinical success using drugs that target Aβ at the earliest stages of AD, we believe that our findings can help to improve upon the effectiveness of such drugs and greatly improve the livelihood of Alzheimer's patients.

Data: CORDIS, © European Union