title: Pan-amyloid oligomer specific scFv antibody attenuates memory deficits and brain amyloid burden in mice with Alzheimer's disease.
abstract: Amyloid oligomers have a critical function in the pathologic processes of various amyloidoses, such as Alzheimer's disease (AD), Parkinson disease (PD), Huntington's disease, prion-related diseases, type 2 diabetes, and hereditary renal amyloidosis. Our previous reports demonstrated that a conformation-dependent oligomer-specific single-chain variable fragment (scFv) antibody, W20, isolated from a naïve human scFv library, can recognize oligomers assembled from α-synuclein, amylin, insulin, Aβ40/42, prion peptide 106-126, and lysozyme, inhibit the aggregation of various amyloid, and attenuate amyloid oligomer-induced cytotoxicity In vitro. Furthermore, W20 recognized the amyloid oligomers in all types of plaques, Lewy bodies, and amylin deposits in the brain tissues of AD and PD patients and in the pancreas of type 2 diabetes patients. In the current study, we showed that W20 blocked the binding of Aβ oligomers to SH-SY5Y cells, did not bind to heat shock protein, rescued cognitive impairments in APP/PS1 transgenic mice, and interfered with Aβ levels and deposits in mouse brain. These results suggest that W20 may be a promising therapeutic for the treatment of AD.
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.forename: Shao-wei
authors.initials: SW
authors.lastname: Wang
authors.forename: Yu-jiong
authors.initials: YJ
authors.lastname: Wang
authors.forename: Ran
authors.initials: R
authors.lastname: Zhang
authors.forename: Ya-nan
authors.initials: YN
authors.lastname: Li
authors.forename: Ya-jing
authors.initials: YJ
authors.lastname: Su
authors.forename: Wei-wei
authors.initials: WW
authors.lastname: Zhou
authors.forename: Xiao-lin
authors.initials: XL
authors.lastname: Yu
authors.affiliation: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China. rtliu@home.ipe.ac.
authors.forename: Rui-tian
authors.initials: RT
authors.lastname: Liu
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D000682:Amyloid / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000276:immunology / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008569:Memory Disorders / Q000378:metabolism / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D058225:Plaque, Amyloid / Q000473:pathology / Q000628:therapy; D053764:Presenilin-1 / Q000276:immunology; D057127:Single-Chain Antibodies / Q000276:immunology* / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: C545487:APP protein, human; D000682:Amyloid; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D006360:Heat-Shock Proteins; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; D057127:Single-Chain Antibodies; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)