Immunotherapeutic efficiency of a tetravalent Aβ1-15 vaccine in APP/PS1 transgenic mice as mouse model for Alzheimer's disease.

Immunization with synthetic, preaggregated β-amyloid (Aβ) was the first treatment approach able to dramatically reduce brain Aβ pathology in Alzheimer's disease (AD) animal models. For the development of a safe vaccine, we investigated whether 4Aβ1-15 (four tandem repeats of GPGPG-linked Aβ1-15 sequences) had therapeutic effects in the APP/PS1 transgenic mice model of AD. We described the production of anti-Aβ antibodies in APP/PS1 mice immunized with 4Aβ1-15 mixed with MF59 adjuvant. The anti-Aβ antibody concentrations were increased which bound to AD plaques, markedly reduced Aβ pathology in transgenic AD mice and levels of intracerebral Aβ (soluble and insoluble), whereas increased serum Aβ levels. Immunization via 4Aβ1-15 (mainly of the IgG1 Class) may induce a non-inflammatory Th2 reaction. Immunohistochemistry analysis of MHC Class II and CD45 revealed that microglial cells were in a less activated state. Of note, 4Aβ1-15-immunized mice showed improved acquisition of memory compared with controls in a reference-memory Morris water-maze behavior test. The data identify the novel immunogen 4Aβ1-15 as a promising new tool for AD immunotherapy.