Although the precise mechanisms and extents of contribution remain unclear, it is widely accepted that oligomeric Aβ and hyperphosphorylated Tau fibrils along with excitotoxicity, neuroinflammation and abortive cell cycle entry and a variety of other cellular disturbances, including impaired cholinergic signaling [46], ER stress [47,48], disrupted autophagic clearance of protein aggregates [49,50,51,52,53], mitochondrial dysfunction [54], oxidative stress [55], and deregulation of iron metabolism [56] combine to cause progressive synaptic failure and neuronal death in the AD brain. This evidence concerns the gene MAPT and Alzheimer disease.