In this project, we will amplify disease-specific αSyn seeds extracted from Lewy body disease (LBD) brains (Uemura, Nat Commun. 2023) and inject them into the brains of mice expressing only human αSyn to develop a novel LBD model. Moreover, we will establish a method to use αSyn extracted from LBD mouse brains as next-generation αSyn seeds. We will perform high-resolution structural analysis on these αSyn seeds and amplified αSyn fibrils by cryo-EM. In addition, we will develop a method to visualize in-tissue αSyn filaments in LBD mouse brains and elucidate their cytotoxic effects.