Skip to main content
Dryad

Data and code from: Diversity of Aβ aggregates produced in a gut-based Drosophila model of Alzheimer’s disease

Brorsson, Ann-Christin1; Elovsson, Greta1; Klingstedt, Therese1; Nilsson, Peter1

Published Aug 20, 2026 on Dryad. https://doi.org/10.5061/dryad.b2rbnzssq

Data files

Aug 20, 2026 version files 445.90 KB

Click names to download individual files

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disease manifested by memory loss and premature death. One major histopathological hallmark of AD is the amyloid plaques formed by aggregates of the amyloid-β (Aβ) peptide and the Aβ aggregation process results in amyloid fibrils with different structures. Herein, we investigate the heterogeneity of Aβ aggregates produced by Drosophila melanogaster expressing the Aβ1-42 peptide with the Arctic mutation E22G (Arctic flies) or a dimeric construct of Aβ1-42 (T22Aβ1-42 flies) in the digestive tract. Staining of the gut of the flies using luminescent conjugated oligothiophenes (LCOs) revealed that the amount of Aβ aggregates increased in both genotypes with age. The LCOs also exhibited distinct staining patterns in the flies. The expression of T22Aβ1-42 resulted in a heavier Aβ load compared to Aβ1-42 with the Arctic mutation. Since the genotypes have similar median survival times, the result indicates that the toxicity of the combined number of aggregates in the Arctic flies is higher compared to the T22Aβ1-42 flies. Stability measurements showed that the most accumulated Aβ species in the Arctic and the T22Aβ1-42 flies were found in the 4 M and 5 M Gua-HCl-fraction, respectively. This indicates that prefibrillar Aβ aggregates constitute the toxic species in Arctic flies while the cause of death in T22Aβ1-42 flies might be the massive load of insoluble aggregates. The study shows that even though the different Aβ peptides resulted in an equal reduction of the lifespan, they formed an array of different aggregates confirming the heterogeneity of this process. Overall, our findings support that distinct Aβ aggregates can exhibit different pathological effects, and we foresee that our Drosophila models can potentially aid in identifying anti-Aβ agents targeting different types of aggregated Aβ species.