MAPT and Alzheimer disease: Neuroscientific studies of TNF-α have revealed a potentially complex biphasic role: administration of anti-TNF-α antibodies i.c.v. decreased Aβ, tau hyper-phosphorylation and memory deficits in AD-related models (Medeiros et al., 2007, Shi et al., 2011) but crossing of 3xTgAD mice with TNFR1/R2 double knockout mice actually exacerbated amyloid and Tau pathology and microglia from these mice had impaired phagocytic ability (Montgomery et al., 2011).