Inflammatory processes in AD are primarily triggered by the up-regulation of the complement system in response to misfolded and aggregated proteins or mislocalized nucleic acids and reactive microglia. Notably, the pro-inflammatory complement factor C5a and its receptor have been found to be up-regulated in microglia in the immediate surroundings of cerebral amyloid plaques in different mouse models of AD.  Previous studies found that the blockage of C5aR by the antagonist PMX205 lead to a therapeutic benefit in a rat model of neurodegeneration. This inhibitor was also tested in Tg2576 and 3xTg mice, two different mouse models of AD, and showed improved memory skills and reduced amyloid plaque formation.   In this study the authors tested the efficacy of active immunization with C5a-peptides  AFF1 and AFF2 in Tg2576 mice exhibiting either early or late stages of the AD-like disease. The authors observed that Tg2576 mice vaccinated at early stages of the disease showed significantly improved contextual memory accompanied by the reduction of microglia activation in the hippocampus and cerebral amyloid plaque load compared to control mice. Late-stage immunization also showed a decrease in the number of activated microglia, and improved memory function, however, had no influence on the amyloid β load. The authors speculate that active immunotherapy against complement factor C5a may be a new and effective approach for the treatment of AD-like disease