In addition to the loss of synapses and neurons (manifesting as brain atrophy), AD involves two neuropathological hallmarks: (1) the formation of neurofibrillary tangles (NFTs) that result from the intracellular aggregation of hyperphosphorylated tau protein, also a characteristic of other neurodegenerative disorders including frontotemporal dementia (FTD), and (2) the development of amyloid plaques, which are extracellular deposits composed mainly of β-amyloid (Aβ) protein that have been the focus of extensive efforts in drug discovery. This evidence concerns the gene MAPT and Alzheimer disease.