A coimmunization vaccine of A?42 ameliorates cognitive deficits without brain inflammation in an Alzheimer's disease model.

ABSTRACT: INTRODUCTION: Vaccination against amyloid-? protein (A?42) induces high levels of antibody, making it a promising strategy for treating Alzheimer's disease (AD). One drawback in the past was that clinical trial approval was withheld because of speculation that the A?42 vaccine induces CD4(+) T cell infiltrations into the central nervous system. To reduce T-cell activation while concomitantly maintaining high anti-A?42 titers is a great challenge in immunology. METHODS: We aimed to demonstrate that coimmunization with A?42 protein and expression plasmid can be beneficial in a mouse AD model and can prevent inflammation. We immunized the AD mice with the coimmunization vaccine and assessed behavior change and A?42 deposition. Furthermore, to determine the safety of the coimmunization vaccine, we used an induced A?42-EAE model to mimic the meningoencephalitis that happened in the AN-1792 vaccine clinical phase II trial and tested whether the coimmunization vaccine could ameliorate T-cell-mediated brain inflammation. RESULTS: The coimmunization vaccination reduced A? plaques and significantly ameliorated cognitive deficit while inhibiting T-cell-mediated brain inflammation and infiltration. These studies demonstrate that the coimmunization strategy that we describe in this article can ameliorate AD pathology without notable adverse effects in mice. CONCLUSIONS: A coimmunization strategy leading to the development of a safe immunotherapeutic/preventive protocol against AD in humans is warranted.

SUBMITTER: Wang S 

PROVIDER: S-EPMC4075150 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature