Although tau abnormality has long been observed in AD, as exemplified by the formation of NFTs by tau that accompany plaque pathology, and tau abnormality can cause neurodegeneration in the absence of plaque pathology as in frontotemporal dementia cases [57, 58], the direct involvement of tau in Aβ-induced synaptic and dendritic spine pathology may initially appear surprising, since tau is generally considered a presynaptic protein that is primarily localized to axons. Here, MAPT is linked to Alzheimer disease.