The present study was the first, to the best of our knowledge, to demonstrate a crucial role of C5a-C5aR-C5aRA action in the pathogenesis of AD, suggesting that C5aRA inhibited AD in mice by suppressing the C5aR-mediated cascade action of mast cells and providing a rationale for the potential use of C5aRA in clinical practice for AD. The gene discussed is C5AR1; the disease is Alzheimer disease.