Research On Capacity Of Murine β-amyloid Oligomerization

Alzheimer’s disease(Alzheimer Disease, AD) is a kind of irreversible progressive neurodegenerative disorder. Although the pathogenesis of AD is still unclear, it has been clear that Amyloid beta(Aβ) protein is one of the most important pathogenic factors to cause Alzheimer’s disease. Aβ is a deduced protein with 38 to 43 amino acids and its two major forms of toxicity are Aβ40 and Aβ42. Besides, according to the current study, Aβ42 has both stronger ability of oligomerization and neurotoxicity, compared with human Aβ40. Therefore, some study suggests that the toxicity of Aβ is related to its ability of oligomerization. In recent years, although there have a lot of researchs to study the toxicity mechanism of Aβ, the way how Aβ plays its toxicity is still unclear.By comparison, human Aβ42 and murine Aβ42 have there different amino acid structures, which are 5, 10 and 13. And the previous cell culture experiments have demonstrated that human Aβ42 has toxicity while murine Aβ42 has little toxicity or even does not have toxicity. Considering the differences in toxicity between human Aβ42 and murine Aβ42 as well as the previous view that the toxicity of Aβ is related to its ability of oligomerization, we can suspect that the low toxicity and even nontoxicity of murine Aβ42 are related to its ability of oligomerization, and the three different amino acid structures of murine Aβ42 are important factors to cause its ability of oligomerization. In addition, the previous studies have not mentioned the comparison of oligomerization between human Aβ42 and murine Aβ42.Therefore, in order to test murine Aβ42’s ability of oligomerization and to testify the impacts of the three different amino acid structures on its ability of oligomerization, the author will apply a series of methods to test human Aβ42’s and murine Aβ42’s ability of oligomerization, with aiming to compare the ability of oligomerization between human Aβ42 and murine Aβ42, and to find the differences with membrane-lipid interactions. The numerous methods include electrophoresis, silver staining, Western-Blot, transmission electron microscopy as well as the monolayer and liposome systems, etc. The results of this research manifest that human Aβ42 and murine Aβ42 have very similar ability of oligomerization, but further experiments are still needed to explore why they have different toxicity. The results of this research will provide a fine reference for the comparison of toxicity between human Aβ42 and murine Aβ42, and offer new evidence for the research of AD.