title: Vaccine Development to Treat Alzheimer's Disease Neuropathology in APP/PS1 Transgenic Mice.
abstract: 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 Aβ(1-42) 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.
authors.affiliation: Department of Neurosciences, EuroEspes Biotechnology, Polígono de Bergondo, Nave F, 15165 A Coruña, Spain.
authors.forename: Iván
authors.initials: I
authors.lastname: Carrera
authors.forename: Ignacio
authors.initials: I
authors.lastname: Etcheverría
authors.forename: Lucía
authors.initials: L
authors.lastname: Fernández-Novoa
authors.forename: Valter
authors.initials: V
authors.lastname: Lombardi
authors.forename: Ramón
authors.initials: R
authors.lastname: Cacabelos
authors.forename: Carmen
authors.initials: C
authors.lastname: Vigo