Development and characterization of a TAPIR-like mouse monoclonal antibody to amyloid-beta.
Tissue amyloid plaque immuno-reactive (TAPIR) antibody was better related to the effect of immunotherapy in Alzheimer's disease (AD) than ELISA antibody. Here we used a hybridoma technique to develop a TAPIR-like anti-human amyloid-beta (Abeta) mouse monoclonal antibody. The obtained monoclonal antibody, 3.4A10, was an IgG2b isotype and recognized N-terminal portion of Abeta1-42 without binding denatured or native amyloid-beta protein precursor. It had higher affinity to Abeta1-42 than to Abeta1-40 by Biacore affinity analysis and stained preferably the peripheral part of senile plaques and recognized the plaque core less than 4G8. It inhibited the Abeta1-42 fibril formation as well as degraded pre-aggregated Abeta1-42 peptide in a thioflavin T fluorescence spectrophotometry assay. The in vivo studies showed that 3.4A10 treatment decreased amyloid burden compared to the control group and significantly reduced Abeta42 levels rather than Abeta40 levels in brain lysates as well as the Abeta*56 oligomer (12mer) in TBS fraction of the brain lysates. 3.4A10 entered brain and decorated some plaques, which is surrounded by more Iba1-positive microglia. 3.4A10 therapy did not induce lymphocytic infiltration and obvious increase in microhemorrhage. We conclude that 3.4A10 is a TAPIR-like anti-human amyloid monoclonal antibody, and has a potential of therapeutic application for AD.
Department of Vascular Dementia Research, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, 36-3 Genko, Morioka, Obu, Aichi, Japan.
Jun
J
Wang
Hideo
H
Hara
Takao
T
Makifuchi
Takeshi
T
Tabira
D000544:Alzheimer Disease / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D000918:Antibody Specificity / Q000276:immunology; D001921:Brain / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006825:Hybridomas; D007132:Immunoglobulin Isotypes / Q000276:immunology; D007167:Immunotherapy / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology*; D058225:Plaque, Amyloid / Q000276:immunology*
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D007132:Immunoglobulin Isotypes; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)