Abeta42 immunization in Alzheimer's disease generates Abeta N-terminal antibodies.
Serum samples from Alzheimer's disease (AD) patients immunized with Abeta42 (AN1792) were analyzed to determine the induced antibody properties including precise amyloid-beta peptide (Abeta) epitopes and amyloid plaque-binding characteristics. The predominant response in these patients is independent of whether or not meningoencephalitis developed and is against the free amino terminus of Abeta. The immunostaining of amyloid plaques in brain tissue by patient sera is adsorbable by a linear Abeta1-8 peptide, demonstrating that the antibodies are directed predominantly to this epitope and not dependent on Abeta conformations or aggregates specific to plaques. Furthermore, the antibodies are not capable of binding amyloid precursor protein and would be predicted to be competent in facilitating clearance of amyloid plaques in AD brains.
Lee
Michael
M
Elan Pharmaceuticals, Inc., So. San Francisco, CA 94080, USA.
Bard
Frederique
F
Johnson-Wood
Kelly
K
Lee
Celeste
C
Hu
Kang
K
Griffith
Sue G
SG
Black
Ronald S
RS
Schenk
Dale
D
Seubert
Peter
P
D000544:Alzheimer Disease / Q000276:immunology / Q000517:prevention & control*; D016229:Amyloid beta-Peptides / Q000008:administration & dosage* / Q000276:immunology* / Q000378:metabolism; D000918:Antibody Specificity; D015153:Blotting, Western / Q000379:methods; D004306:Dose-Response Relationship, Immunologic; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D007114:Immunization / Q000009:adverse effects / Q000379:methods*; D007150:Immunohistochemistry / Q000379:methods; D008590:Meningoencephalitis / Q000097:blood / Q000209:etiology / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism
C437846:AN-1792; D016229:Amyloid beta-Peptides; D000939:Epitopes; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)