APOE and Alzheimer disease: Once in the brain, gingipains cause AD-related changes such as as increase in Aβ and tau accumulation, modulate APP and tau processing, cause microglial activation and proliferation, induce IL-1β, TNF-α and IL-6 secretion, cleave APOE proteins, and induce neuronal degeneration and synapse loss [336, 346–348, 352].