APOE4 has a clear effect of promoting neuroinflammation in tauopathy, as we and others have shown that it promotes microgliosis and astrogliosis in mouse models of tauopathy.7,22,23 This connection between APOE4 and inflammation is also present in humans, as analysis of postmortem AD patient samples shows a greater extent of gliosis throughout the brain79 and higher levels of CD68-activated microglia51 in APOE4 than in APOE3 carriers. This evidence concerns the gene CD68 and Alzheimer disease.