Continuous vaccinations of 4Aβ1-15 induces specific fluctuation of inflammatory factors accompany with pathologic alterations alleviation in APP/PS1 mice

Abstract

The common pathological hallmark of Alzheimer’s disease (AD) is β-amyloid plaques deposition. Immunotherapy is a revolutionary pharmacological treatment for AD, aiming at improving plaque clearance while concomitantly decreasing inflammation. Our previous study prepared antigen 4Aβ1-15 and found that it could alleviate pathologic alterations in APP/PS1 transgenic mice. The objective of our study was to research the changing processes induced by immunotherapy, including the inflammatory factor levels and microglial activation that is closely associated with Ab burdens clearance. APP/PS1 mice were injected with 4Aβ1-15 6 times. Each time, the inflammatory factors in sera were detected, and a specific fluctuation that first increased and then decreased was found, in which there was a turning point after the third injection. It prompted us to further detect the indicators in the brains after the third injection and the sixth injection. The results showed that the therapeutic effects for Ab burdens and behaviors were continuously improved during the whole immune processes, whereas the inflammatory factor levels and microglial activation experienced similar specific fluctuations. The novel discovery may provide convenient methods for further detection and evaluation of immunotherapy in disease courses.