Genetic studies have shown that early onset AD is caused by dominantly inherited mutations in APP, MAPT, MPSEN1, and PSEN2. The functional implications of these risk genes strongly suggest the amyloid cascade hypothesis, which postulates that changes in Aβ homeostasis lead to the aggregation and deposition of Aβ and, eventually, to the pathological conditions of AD. Here, MAPT is linked to Alzheimer disease.