A novel recombinant 6A?15-THc-C chimeric vaccine (rCV02) mitigates Alzheimer's disease-like pathology, cognitive decline and synaptic loss in aged 3?×?Tg-AD mice.

ABSTRACT: Alzheimer's disease (AD) is a neurodegenerative disorder that impairs memory and cognition. Targeting amyloid-? (A?) may be currently the most promising immunotherapeutic strategy for AD. In this study, a recombinant chimeric 6A?15-THc-C immunogen was formulated with alum adjuvant as a novel A? B-cell epitope candidate vaccine (rCV02) for AD. We examined its efficacy in preventing the cognitive deficit and synaptic impairment in 3?×?Tg-AD mice. Using a toxin-derived carrier protein, the rCV02 vaccine elicited robust A?-specific antibodies that markedly reduced AD-like pathology and improved behavioral performance in 3?×?Tg-AD mice. Along with the behavioral improvement in aged 3?×?Tg-AD mice, rCV02 significantly decreased calpain activation concurrent with reduced soluble A? or oligomeric forms of A?, probably by preventing dynamin 1 and PSD-95 degradation. Our data support the hypothesis that reducing A? levels in rCV02-immunized AD mice increases the levels of presynaptic dynamin 1 and postsynaptic PSD-95 allowing functional recovery of cognition. In conclusion, this novel and highly immunogenic rCV02 shows promise as a new candidate prophylactic vaccine for AD and may be useful for generating rapid and strong A?-specific antibodies in AD patients with pre-existing memory Th cells generated after immunization with conventional tetanus toxoid vaccine.

SUBMITTER: Yu YZ 

PROVIDER: S-EPMC4891678 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature