Vaccine Development to Treat Alzheimer’s Disease Neuropathology in APPPS1 Transgenic Mice

Abstract EN

A novel vaccine addressing the major hallmarks of Alzheimer’s disease (AD), senile plaque-like deposits of amyloid beta-protein (Aβ), neurofibrillary tangle-like structures, and glial proinflammatory cytokines, has been developed.

The present vaccine takes a new approach to circumvent failures of previous ones tested in mice and humans, including the Elan-Wyeth vaccine (AN1792), which caused massive T-cell activation, resulting in a meningoencephalitis-like reaction.

The EB101 vaccine consists of Aβ1-42 delivered in a novel immunogen-adjuvant composed of liposomes-containing sphingosine-1-phosphate (S1P).

EB101 was administered to APPswe/PS1dE9 transgenic mice before and after AD-like pathological symptoms were detectable.

Treatment with EB101 results in a marked reduction of Aβ plaque burden, decrease of neurofibrillary tangle-like structure density, and attenuation of astrocytosis.

In this transgenic mouse model, EB101 reduces the basal immunological interaction between the T cells and immune activation markers in the affected hippocampal/cortical areas, consistent with decreased amyloidosis-induced inflammation.

Therefore, immunization with EB101 prevents and reverses AD-like neuropathology in a significant manner by halting disease progression without developing behavioral spatial deficits in transgenic mice.