Seed-Induced Accumulation of β-Amyloid Exacerbates Oxidative Stress in Drosophila

Abstract

Background: Progression of Alzheimer's disease (AD) was considered involving fibrosis and amyloidosis of abnormal proteins that kill cells and disrupt neuronal connections. The polymerization process of Amyloid β (Aβ) is resistant to degradation. Aβ42, one of the major isoforms of Aβ, could be a "seed" to accelerate the aggregation and deposition of homologous or heterologous erroneous proteins in the brain. Methods: A new drosophila model was constructed by exogenous injection of Aβ42 to explore the neural mechanism of amyloid plaque formation in the brain. Results: Aβ aggregates in the brains of APP-injected flies decreased in the early stage and increased in the later stage, suggesting that Aβ42 may act as an innate immune defense molecule to activate brain immune responses to protect the host from infection. To demonstrate the effect of exogenous injections on antioxidant capacity, reactive oxygen species (ROS) were measured in a drosophila model. It was found that injection of Aβ42 accelerated ROS accumulation in the brain only in the short term, but ROS accumulated and accelerated Aβ accumulation in brain-induced neurodegeneration over time. Both crawling ability tests and lifespan tests showed more severe AD symptoms. However, in the monitoring of fly sleep after Aβ42 injection, sleep was compensated in APP flies injected with Aβ42. Conclusion: A seed mechanism is involved in the propagation and development of Aβ in the brain of Drosophila. It also provides new insights into Alzheimer's disease research.