Identification of structural variations in the carboxyl terminus of Alzheimer's disease-associated beta A4[1-42] amyloid using a monoclonal antibody.
The accumulation of amyloid plaques and amyloid congophilic angiopathy (ACA) in the brains of affected individuals is one of the main pathological features of Alzheimer's disease. Within these deposits, the beta A4 (Ass) polypeptide represents a major component with the C-terminal 39-43 amino acid variants being most abundant. Using a mouse IgG1 MoAb produced by hybridoma beta A4[35-43]-95.2 3B9, which reacts with the epitope is defined by the amino acid residues beta A438[GVV]40, this study has identified a unique conformation within the carboxyl terminus of human beta A4[1-42]. Although the beta A438[GVV]40 sequence is present within the C-termini of human beta A4[1-40] and beta A4[1-43] and the beta A4-containing region of human APP, the beta A4[35-43]-95.2 3B9 MoAb (designated MoAb 3B9) does not bind these polypeptides, demonstrating a high degree of specificity for the beta A438[GVV]40 epitope as presented within the beta A4[1-42] sequence. The beta A4[1-42] epitope bound by MoAb 3B9 is sensitive to heating (100 degrees C for 5 min) and is denatured by SDS but not by oxidative radio-iodination of beta A4 or by adsorption to plastic surfaces or nitrocellulose. The recognition of beta A4 plaque deposits and ACA by MoAb 3B9 within formalin-fixed sections of human AD brain demonstrates the potential of these antibodies for investigating the role of the unique beta A4[1-42] conformation in the development of Alzheimer's disease.
Jayasena
U L
UL
Department of Pathology, The University of Melbourne and Mental Health Research Institute of Victoria, Parkville, Australia.
Gribble
S K
SK
McKenzie
A
A
Beyreuther
K
K
Masters
C L
CL
Underwood
J R
JR
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000276:immunology*; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D018604:Epitope Mapping; D000939:Epitopes; D006801:Humans; D006825:Hybridomas; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000276:immunology*
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D000939:Epitopes; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); C098994:amyloid beta-protein (1-43); C430405:amyloid beta-protein (35-43)