title: Administration of amyloid-β42 oligomer-specific monoclonal antibody improved memory performance in SAMP8 mice.
abstract: Amyloid-β peptide (Aβ) is recognized by many as the leading cause of Alzheimer's disease (AD), and Aβ oligomers play a major role in the early-onset form of AD. Recently, the application of passive immunization targeting Aβ has been investigated as a potential method of AD immunotherapy. We used a strain of monoclonal antibody against Aβ42 oligomers, designated A8, as an Aβ inhibitor to suppress Aβ aggregation and Aβ-derived cell toxicity in vitro, and as a passive immunotherapy approach to treat SAMP8 (senescence accelerated mouse sub-line P8) mice, an animal model of AD, in vivo. First, our results showed that pre-incubation of A8 with Aβ oligomers inhibited both the maturation of Aβ fiber and Aβ oligomer toxicity on SH-SY5Y cells. Second, learning and memory was improved through intraperitoneal administration of A8 in SAMP8 mice. Third, Aβ pathology was ameliorated with decreased Aβ oligomers and phospho-tau levels in SAMP8 mice. Our data suggest that our monoclonal antibody A8 may be a candidate as a potential immunotherapeutic agent in AD.
authors.affiliation: College of Life Sciences and Bioengineering, Beijing Jiaotong University, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jin-Sheng
authors.initials: JS
authors.lastname: He
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Fu-Xiang
authors.initials: FX
authors.lastname: Bao
authors.forename: Si-Yuan
authors.initials: SY
authors.lastname: Pang
authors.forename: Fan
authors.initials: F
authors.lastname: Yin
authors.forename: Hong-Gang
authors.initials: HG
authors.lastname: Hu
authors.forename: Xiang-Lei
authors.initials: XL
authors.lastname: Peng
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Sun
authors.forename: Yan-Peng
authors.initials: YP
authors.lastname: Zheng
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Hou
authors.forename: Tao
authors.initials: T
authors.lastname: Hong
mesh_terms: D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology*
chemical_list: D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)