Effects of tau on Aβ-induced synaptic damage in a Drosophila model of Alzheimer's disease.

Abstract

Objectives: The etiology and pathologic mechanism underlying Alzheimer's disease (AD) are not clear. This study determined the effects of tau on amyloid-beta peptide(Aβ)-induced synaptic damages in a Drosophila model of AD.

Methods: Galactose-regulated upstream promoter element 4(Gal4) and an upstream active sequence system was used to establish four kinds of Aβ transgenic Drosophila models of AD. Behavioral evaluation and immunohistochemical localization were performed in Aβ transgenic Drosophila models. Tau mutants were introduced into arctic mutant Aβ1-42 (arctic mutant Aβ [Aβarc]) Drosophila. The P{Gal4}A307 Drosophila strain was used as a control group; 12 strains were obtained to determine the effects of tau with or without Aβarc. Electrophysiologic records of the tau mutant groups were created.

Results: The flight and crawling ability of Aβ transgenic Drosophila were gradually weakened compared to the control group, and the life span was significantly shorter than the control group. Aβ was specifically expressed in the Drosophila giant fiber pathway and further accumulated in neuronal cell bodies based on immunohistochemistry. The percentage of the excitatory junctional potential (EJP) response in transgenic Drosophila expressing Aβarc was significantly decreased, which was approximately 40% lower than the control group. The tau deletion mutation alleviated the synaptic transmission disorder caused by Aβ and improved the viability of Drosophila.

Conclusion: The tau deletion mutation significantly improved the synaptic damage caused by Aβ, and tau protein played an indispensable role in the synaptic dysfunction caused by Aβ, suggesting that Aβ and tau have close interactions in the pathogenesis of AD.