Duration and Specificity of Humoral Immune Responses in Mice Vaccinated with the Alzheimer's Disease-Associated �-Amyloid 1-42 Peptide

Dickey, Chad A.; Morgan, David G.; Kudchodkar, Sagar; Weiner, David B.; Bai, Yun; Cao, Chuanhai; Gordon, Marcia N.; Ugen, Kenneth E.
November 2001
DNA & Cell Biology;Nov2001, Vol. 20 Issue 11, p723
Academic Journal
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by overproduction of �-amyloid (A�), which is formed from amyloid precursor protein (APP), with the subsequent pathologic deposition of A� in regions of the brain important for memory and cognition. Recently, vaccination of murine models of AD that exhibit A� 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 A� 1-42 peptide protects these mice from the memory deficits they would ordinarily develop. This report further characterizes the A� 1-42 peptide vaccine in mice. Anti-A� response time course analysis indicated that at least three vaccinations (each 100 �g) were necessary to elicit a significant anti-A� 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 A� peptide. Also, measurement of specific murine Ig isotypes in A�-vaccinated mice demonstrated a predominant IgG[sub 1] and IgG[sub 2b] response, suggesting a type 2 (Th2) T-helper cell immune response, which drives humoral immunity. Finally, lymphocyte proliferation assay experiments using A� peptides and splenocytes from vaccinated mice demonstrated that the vaccine specifically stimulates T-cell epitopes present within the A� peptide.


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