title: A novel monoclonal antibody specific for the amino-truncated beta-amyloid Abeta5-40/42 produced from caspase-cleaved amyloid precursor protein.
abstract: Deposition of beta-amyloid peptide (Abeta) as senile plaques and amyloid angiopathy are the major neuropathological features of Alzheimer's disease (AD). Heterogeneity is observed in the N- and C-termini of the deposited Abeta species. Recent evidence implicates caspase activation and apoptosis in AD neurodegeneration. We previously reported that a distinct N-terminally truncated Abeta species, Abeta5-40/42 is preferentially produced from the caspase-cleaved form of amyloid precursor protein (APP) lacking its C-terminal 31 amino acids and that it is deposited in AD brain tissues. Here, we generated a novel monoclonal antibody specific to the N-terminal end of Abeta5-40/42. Western blotting confirmed that this antibody recognizes Abeta5-40 but not Abeta1-40. We also showed that the antibody is able to immunoprecipitate Abeta5-40 but not Abeta1-40. Immunoprecipitation with the antibody followed by mass spectrometric analysis further detected Abeta5-40 in the conditioned media from neuroblastoma cells expressing the caspase-cleaved APP. The antibody reacted weakly with Abeta derived from AD brains. These results suggest that our novel monoclonal antibody is useful for detecting the N-terminally truncated Abeta produced in conjunction with caspase activation.
authors.affiliation: Department of Demyelinating Disease and Aging, National Institute of Neuroscience, NCNP, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Kiyoko S
authors.initials: KS
authors.lastname: Murayama
authors.forename: Fuyuki
authors.initials: F
authors.lastname: Kametani
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tabira
authors.forename: Wataru
authors.initials: W
authors.lastname: Araki
mesh_terms: D016229:Amyloid beta-Peptides / Q000276:immunology*; D016564:Amyloid beta-Protein Precursor / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001921:Brain / Q000276:immunology*; D020169:Caspases / Q000276:immunology*; D005260:Female; D007118:Immunoassay / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000276:immunology*; D058255:Protease Nexins; D011956:Receptors, Cell Surface / Q000276:immunology*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000911:Antibodies, Monoclonal; D010446:Peptide Fragments; D058255:Protease Nexins; D011956:Receptors, Cell Surface; C500436:amyloid beta-peptide (5-40); C500437:amyloid beta-peptide (5-42); D020169:Caspases