MAPT and Alzheimer disease: In contrast, NFTs, of which the majority of tau is aberrantly phosphorylated and misfolded, lead to synaptic alterations and correlate with neuronal loss and cognitive deficits in AD patients more readily than does amyloid burden (Lewis et al., 2000; Jose Metcalfe et al., 2010; Nelson et al., 2012; Thompson and Vinters, 2012).