According to the Alzheimer Disease (AD) amyloid hypothesis, the deposition of prefibrillar and fibrillar alpha-beta peptide sets off pathogenic cascades of neuroinflammation and neurodegeneration that lead to synaptic and neuronal loss and cognitive decline. The complement cascade has been found to modulate the disease even though the mechanism of action is highly controversial. Animal experiments in the AD mouse model show that inhibition of the complement component C5a (a terminal product of complement activation) reduces amyloid and alleviates the pathology. Macrophages and neutrophils carry C5a receptors. In the mouse model for ATTR V30M neuropathy, C5a receptor inhibition exacerbates amyloid deposition while administration of the full C5a agonist significantly reduces amyloid deposition. Yet, inhibition of the C5a receptor in the AD mouse model resulted in the decrease of amyloid deposition. We believe the difference may lie in the fact that in TTR amyloidosis the amyloidogenic peptides are imported from the circulation (produced in the liver), while in AD the alpha-beta peptides are locally produced so that prolonged C5a stimulation may actually increase production of alpha-beta due to the increase in inflammation. C5a receptor agonists have not been fully tested in AD and we hypothesize, based on preliminary data, that in fact they will have a beneficial effect by clearing amyloid. Thus, a modified C5a receptor agonist along with a C5a receptor antagonist will be intermittently administered to AD mice by mouth. Following the completion of the treatment protocols, Thioflavin S, immunofluorescence, ELISA, immunoblotting, gene expression assays and cognitive testing will be carried out to evaluate the effects of the aforementioned therapeutic molecules on the pathophysiology of the disease.