Human antibodies reactive with beta-amyloid protein in Alzheimer's disease.
Four human B cell lines established by Epstein-Barr viral transformation of B cells from a patient with a clinical diagnosis of Alzheimer's disease (AD) were found to secrete antibodies that react with plaques and cerebrovascular blood vessels in AD brain in a staining profile characteristic of beta-amyloid protein (beta-AP) in AD brain. Two of these antibodies were shown to be reactive with a rare plaque in a normal brain. In these studies, immunofluorescence and avidin-biotin complex immunoperoxidase methodology were used to determine antibody reaction, and thioflavine S was used to double label amyloid and neurofibrillary tangles. The four antibodies also reacted with neurons in normal and AD brain. Absorption studies, dot immunoblots, and enzyme-linked immunosorbent assays with beta-amyloid peptides 1-28 (beta-A1-28) and 1-40 (beta-A1-40) indicate the major determinant of the reactive epitope is located in the region of amino acids 1-28 of beta-AP. However, inhibition studies demonstrate a significant contribution to the antigenic determinant by the 29-40 region of the beta-A1-40. These antibodies represent the first human autoantibodies against beta-AP. The pathological significance of these autoantibodies is discussed.
Gaskin
F
F
Department of Psychiatry, University of Virginia School of Medicine, Charlottesville 22908.
Finley
J
J
Fang
Q
Q
Xu
S
S
Fu
S M
SM
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000276:immunology*; D016229:Amyloid beta-Peptides / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D001921:Brain / Q000276:immunology; D002461:Cell Line, Transformed; D003720:Densitometry; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D001323:Autoantibodies