As recently reviewed by Jadhav and collaborators [76], several factors point strongly towards a prominent role of presynaptic tau protein in mediating synaptic pathology, including (1) cognitive decline that best correlates with synaptic loss and synaptic failure; (2) synapse loss in parallel with NFT formation and occurring in the same regions in AD brains; and (3) higher NFT count associated with lower levels of presynaptic proteins in AD. This evidence concerns the gene MAPT and Alzheimer disease.