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

Immunization with synthetic, preaggregated -amyloid (A) was the first treatment approach able to dramatically reduce brain A pathology in Alzheimer's disease (AD) animal models. For the development of a safe vaccine, we investigated whether 4A1-15 (four tandem repeats of GPGPG-linked A1-15 sequences) had therapeutic effects in the APP/PS1 transgenic mice model of AD. We described the production of anti-A antibodies in APP/PS1 mice immunized with 4A1-15 mixed with MF59 adjuvant. The anti-A antibody concentrations were increased which bound to AD plaques, markedly reduced A pathology in transgenic AD mice and levels of intracerebral A (soluble and insoluble), whereas increased serum A levels. Immunization via 4A1-15 (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, 4A1-15-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 4A1-15 as a promising new tool for AD immunotherapy.