期刊
NEUROBIOLOGY OF DISEASE
卷 39, 期 3, 页码 301-310出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2010.04.014
关键词
Alzheimer's disease; Immunotherapy; Amyloid beta; Large animal model; Aged beagles; Conformational antibodies
资金
- National Institutes of Health [NIA-AG20242, NIA-AG20241, NIA-AG00538, NINDS-NS50895, NIA-AG031764]
- NIH/NIA [P50 AG16573]
Previously we showed that anti-A beta, peptide immunotherapy significantly attenuated Alzheimer's-like amyloid deposition in the central nervous system of aged canines. In this report we have characterized the changes that occurred in the humoral immune response over 2.4 years in canines immunized repeatedly with aggregated A beta(1-42) (AN1792) formulated in alum adjuvant. We observed a rapid and robust induction of anti-A beta, antibody titers, which were associated with an anti-inflammatory T helper type 2 (Th2) response. The initial antibody response was against dominant linear epitope at the N-terminus region of the A beta(1-42) peptide, which is identical to the one in humans and vervet monkeys. After multiple immunizations the antibody response drifted toward the elevation of antibodies that recognized conformational epitopes of assembled forms of A beta and other types of amyloid. Our findings indicate that prolonged immunization results in distinctive temporal changes in antibody profiles, which may be important for other experimental and clinical settings. (C) 2010 Elsevier Inc. All rights reserved.
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