Both Aβ and ageing trigger an increase in pro-inflammatory cytokines, including the master regulator of inflammation TNF-α,46 and TNF-α is known to mediate the inhibition of LTP by Aβ59-61 and ageing.62 Furthermore, tau triggers pro-inflammatory states, which are associated with increased TNF-α levels.63,64 Because TNF-α can promote certain forms of LTD, via activation of TNFR1,59,65 we hypothesized that TNF-α would be required for Alzheimer’s disease brain tau- and Aβ-facilitated LTD. Here, MAPT is linked to early-onset autosomal dominant Alzheimer disease.