ArticlePloS one2015
Systematic Aβ Analysis in Drosophila Reveals High Toxicity for the 1-42, 3-42 and 11-42 Peptides, and Emphasizes N- and C-Terminal Residues.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed.
- Intracellular Aβ42 Sequestration by a Serine Protease Mitigates Neurotoxicity in a Drosophila Alzheimer's Disease Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Dynamic changes in neuronal and glial GAL4 driver expression during Drosophila aging.Genetics · 2025Article
- Article
- A NovelInternational journal of molecular sciences · 2024Article
- The ubiquitin thioesterase YOD1 ameliorates mutant Huntingtin induced pathology in Drosophila.Scientific reports · 2023Article
- HSP10 as a Chaperone for Neurodegenerative Amyloid Fibrils.Frontiers in neuroscience · 2022Article
- Exploring Aβ Proteotoxicity and Therapeutic Candidates UsingInternational journal of molecular sciences · 2021Review
- Alzheimer's protection effect of A673T mutation may be driven by lower Aβ oligomer binding affinity.Journal of neurochemistry · 2021Article
- Review
- Article
- Amyloid fibril polymorphism: a challenge for molecular imaging and therapy.Journal of internal medicine · 2018Review
- Short Aβ peptides attenuate Aβ42 toxicity in vivo.The Journal of experimental medicine · 2018Article
- Bar-coding neurodegeneration: identifying subcellular effects of human neurodegenerative disease proteins usingDisease models & mechanisms · 2017Article
- Human TTBK1, TTBK2 and MARK1 kinase toxicity inBiology open · 2017Article
- Alternative Selection of β-Site APP-Cleaving Enzyme 1 (BACE1) Cleavage Sites in Amyloid β-Protein Precursor (APP) Harboring Protective and Pathogenic Mutations within the Aβ Sequence.The Journal of biological chemistry · 2016Article
- pGluAβ increases accumulation of Aβ in vivo and exacerbates its toxicity.Acta neuropathologica communications · 2016Article
- AβPP processing results in greater toxicity per amount of Aβ1-42 than individually expressed and secreted Aβ1-42 in Drosophila melanogaster.Biology open · 2016Article
- Comparative pathobiology of β-amyloid and the unique susceptibility of humans to Alzheimer's disease.Neurobiology of aging · 2016Article
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5 authors.
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Abstract
Brain amyloid plaques are a hallmark of Alzheimer's disease (AD), and primarily consist of aggregated Aβ peptides. While Aβ 1-40 and Aβ 1-42 are the most abundant, a number of other Aβ peptides have also been identified. Studies have indicated differential toxicity for these various Aβ peptides, but in vivo toxicity has not been systematically tested. To address this issue, we generated improved transgenic Drosophila UAS strains expressing 11 pertinent Aβ peptides. UAS transgenic flies were generated by identical chromosomal insertion, hence removing any transgenic position effects, and crossed to a novel and robust Gal4 driver line. Using this improved Gal4/UAS set-up, survival and activity assays revealed that Aβ 1-42 severely shortens lifespan and reduces activity. N-terminal truncated peptides were quite toxic, with 3-42 similar to 1-42, while 11-42 showed a pronounced but less severe phenotype. N-terminal mutations in 3-42 (E3A) or 11-42 (E11A) resulted in reduced toxicity for 11-42, and reduced aggregation for both variants. Strikingly, C-terminal truncation of Aβ (1-41, -40, -39, -38, -37) were non-toxic. In contrast, C-terminal extension to 1-43 resulted in reduced lifespan and activity, but not to the same extent as 1-42. Mutating residue 42 in 1-42 (A42D, A42R and A42W) greatly reduced Aβ accumulation and toxicity. Histological and biochemical analysis revealed strong correlation between in vivo toxicity and brain Aβ aggregate load, as well as amount of insoluble Aβ. This systematic Drosophila in vivo and in vitro analysis reveals crucial N- and C-terminal specificity for Aβ neurotoxicity and aggregation, and underscores the importance of residues 1-10 and E11, as well as a pivotal role of A42.
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