amyloid-beta (aβ) d7h mutation increases oligomeric aβ42 and alters properties of aβ-zinccopper assemblies淀粉样β蛋白(aβ)d7h突变增加了寡聚aβ42和改变aβ-zinccopper组件的属性.pdfVIP

Amyloid-Beta (Ab) D7H Mutation Increases Oligomeric Ab42 and Alters Properties of Ab-Zinc/Copper Assemblies 1,7 1,2,3,8 1 1 1 1 Wei-Ting Chen , Chen-Jee Hong , Ya-Tzu Lin , Wen-Han Chang , He-Ting Huang , Jhih-Ying Liao , 6 1 3 4,9 6 1,5 Yu-Jen Chang , Yi-Fang Hsieh , Chih-Ya Cheng , Hsiu-Chih Liu , Yun-Ru Chen *, Irene H. Cheng * 1 Institute of Brain Science, National Yang Ming University, Taipei, Taiwan, 2 Division of Psychiatry, National Yang Ming University, Taipei, Taiwan, 3 Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan, 4 Division of Neurology, National Yang Ming University, Taipei, Taiwan, 5 Brain Research Center, National Yang Ming University, Taipei, Taiwan, 6 Genomics Research Center, Academia Sinica, Taipei, Taiwan, 7 Taiwan International Graduate Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, Taiwan, 8 Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan, 9 Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan Abstract Amyloid precursor protein (APP) mutations associated with familial Alzheimer’s disease (AD) usually lead to increases in amyloid b-protein (Ab) levels or aggregation. Here, we identified a novel APP mutation, located within the Ab sequence (AbD7H), in a Taiwanese family with early onset AD and explored the pathogenicity of this mutation. Cellular and biochemical analysis reveal that this mutation increased Ab production, Ab42/40