Suhail Rasool
University of California, USA
Title: Vaccination against a generic amyloid oligomer epitope improves cognitive function, reduces plaque and tau pathology in Alzheimer’s transgenic mice.
Biography
Biography: Suhail Rasool
Abstract
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 and 3xtg mice, which develop a progressive accumulation of plaques, tangles and cognitive impairment. We vaccinated Tg2576 and 3xTg 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. In addition to cognitive improvement subcutaneous administration of these antigens markedly reduced total plaque load (Aβ burden) and hyper phosphorylated tau (tau pathology). We conclude that amyloid Aß sequence is not necessary to produce a protective immune response as the random peptide (3A) gives rise to an oligomer specific 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.