Ann Christin Brorsson | Insights into Alzheimer’s Disease from

Ann-Christin Brorsson, Linköping University, Sweden Title: Insights into Alzheimer’s Disease from Drosophila Models: Lessons Learned and Future Directions Abstract Drosophila melanogaster is a widely used model for Alzheimer’s disease (AD) research, enabling the study of human Aβ-induced pathology in a genetically tractable, cost-effective, and ethically advantageous system. Key benefits of the model include its short lifespan, powerful genetic toolbox, low maintenance costs, and suitability for large-scale genetic and pharmacological screening. Transgenic flies reproduce several hallmark features of AD, including protein aggregation, oxidative stress, neurodegeneration, and behavioral impairment, making them valuable tools for both mechanistic studies and therapeutic discovery1. Our studies demonstrate that Drosophila models of AD recapitulate key pathological processes, including neuronal cell death, oxidative stress, and age dependent Aβ aggregation, while also revealing distinct mechanisms of toxicity. Comparison of the Aβ and AβPP-BACE1 models showed differences in Aβ1–42 levels, lysosomal and endosomal responses, and the accumulation of AβPP-derived species2. Likewise, gut-specific expression of T22Aβ1–42 or Arctic Aβ1–42 (Fig 1) generated aggregates with distinct loads, structures, and toxic properties3. Notably, Arctic Aβ1–42 aggregates exhibited greater toxicity relative to their abundance and were associated with impaired intestinal barrier integrity and gut leakage. Together, these findings highlight the importance of considering Aβ variant- and model-specific mechanisms when investigating AD pathogenesis and evaluating potential therapeutic strategies. They further underscore the value of Drosophila as a versatile and powerful model for uncovering disease mechanisms and novel therapeutic targets while supporting the principles of Replacement, Reduction, and Refinement (3Rs) in biomedical research. Figure 1: Illustration of the digestive tract of Drosophila. The cutout represents an estimation of the selected area used for fluorescence imaging of Aβ aggregates. 1Elovsson G, Bergkvist L, Brorsson A.-C. (2021) Int. J. Mol. Sci. 22(19):10448. 2 Bergkvist L, Du Z, Elovsson G, Appelqvist H, Itzhaki LS, Kumita JR, Kågedal K & Brorsson A.-C. (2020). FEBS Open Bio. 10(3):338-350. doi: 10.1002/2211-5463.12773. 3 Elovsson G, Klingstedt T, Brown M, Nilsson PR & Brorsson A.-C. (2025. PLoS one 2025, 20(7): e0314832. #ISAD2026 #Alzheimers #Dementia #AlzheimersDisease #DementiaResearch #AlzheimersResearch #Neuroscience #NeurodegenerativeDiseases #BrainHealth #Neuroinflammation #Amyloid #TauProtein #Biomarkers #ClinicalResearch #ScientificConference #MedicalConference #InternationalConference #ResearchCollaboration #Innovinc #InnovincConferences #InnovincInternational #ParisConference