Duration and specificity of humoral immune responses in mice vaccinated with the Alzheimer's disease-associated beta-amyloid 1-42 peptide.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by overproduction of beta-amyloid (Abeta), which is formed from amyloid precursor protein (APP), with the subsequent pathologic deposition of Abeta in regions of the brain important for memory and cognition. Recently, vaccination of murine models of AD that exhibit Abeta deposition has halted or delayed the usual progression of the pathology of AD. Our group has demonstrated that vaccination of a doubly transgenic mouse model (expressing mutant APP and presenilin-1) with the Abeta 1-42 peptide protects these mice from the memory deficits they would ordinarily develop. This report further characterizes the Abeta 1-42 peptide vaccine in mice. Anti-Abeta response time course analysis indicated that at least three vaccinations (each 100 microg) were necessary to elicit a significant anti-Abeta titer. Subsequent vaccinations resulted in half-maximal antibody titers of at least 10,000, and these titers were maintained for at least 5 months after the final boost. Peptide binding competition studies indicated that the highest humoral responses are generated against the N terminus of the Abeta peptide. Also, measurement of specific murine Ig isotypes in Abeta-vaccinated mice demonstrated a predominant IgG(1) and IgG(2b) response, suggesting a type 2 (Th2) T-helper cell immune response, which drives humoral immunity. Finally, lymphocyte proliferation assay experiments using Abeta peptides and splenocytes from vaccinated mice demonstrated that the vaccine specifically stimulates T-cell epitopes present within the Abeta peptide.
Dickey
C A
CA
Alzheimer's Research Laboratory, University of South Florida, Tampa, Florida 33612, USA.
Morgan
D G
DG
Kudchodkar
S
S
Weiner
D B
DB
Bai
Y
Y
Cao
C
C
Gordon
M N
MN
Ugen
K E
KE
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D000818:Animals; D000917:Antibody Formation; D000918:Antibody Specificity; D004797:Enzyme-Linked Immunosorbent Assay; D007136:Immunoglobulins / Q000145:classification; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D017386:Sequence Homology, Amino Acid; D014612:Vaccines / Q000008:administration & dosage*
D016229:Amyloid beta-Peptides; D007136:Immunoglobulins; D010446:Peptide Fragments; D014612:Vaccines; C075222:amyloid beta-protein (1-42)