Vaccination against a generic amyloid oligomer epitope improves cognitive phenotype in Tg2576 mice independent of the peptide antigen sequence
Tuesday, Nov 18, 2008, 8:00 AM - 9:00 AM
, H. M. CORIA
, L. BREYDO
, S. MILTON
, C. GLABE
Mol. Biol. & Biochem.,
Neurol. and Inst. for Brain Aging & Dementia, Univ. of California, Irvine, CA;
Mol. Biol. & Biochem., Univ. of California, Irvine, CA
Accumulation of beta-amyloid (Aß) is an important molecular event in Alzheimer’s disease (AD). It is now well known that vaccination against fibrillar Aß prevents amyloid accumulation and preserves cognitive function in transgenic mouse models. To study the effect of vaccination against generic oligomer epitopes, Aß oligomers, islet amyloid polypeptide (IAPP) oligomers, random peptide oligomer (3A) & Aß fibrils were used to vaccinate Tg2576 mice, which develop a progressive accumulation of plaques and cognitive impairment. We vaccinated Tg2576 mice monthly with the above mentioned vaccines and studied various cognitive parameters at 6 months, 10 months and 14 months of age. We tested escape latency, number of platform crosses in the Morris water maze test (MWM) (which are related to hippocampus), novel object recognition (which is related to cortex) and inhibitory avoidance (which is related to amygdala). It was found that all vaccinated mice have a significant improvement in cognitive function compared to controls. We also find a significant improvement in cognitive functions from 6 months to 14 months old vaccinated mice as compared to controls. At 14 months random peptide oligomers show the same improvement in cognitive phenotype as Aß and IAPP oligomers. We conclude that amyloid Aß sequence is not necessary to produce a protective immune response as the random peptide (3A) gives rise to same immune response. The critical epitope is a pathology-specific conformation of the peptide backbone that is independent of the specific amino acid sequence. It is therefore suggested that vaccination against a non-human amyloid oligomer epitope may be an effective strategy for developing a vaccine that does not have the potential for auto-inflammatory immune complications.
, Kinexis, Inc., F. Consultant/Advisory Board.
BioStar Discovery bio0310375
Larry Hillblom Foundation
[Authors]. [Abstract Title]. Program No. XXX.XX. 2008 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2008. Online.
2008 Copyright by the Society for Neuroscience all rights reserved. Permission to republish any abstract or part of any abstract in any form must be obtained in writing by SfN office prior to publication.
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