MAPT and Alzheimer disease: Whereas in the amyloid cascade hypothesis genetic, pathologic, and biochemical evidence implicate aggregation of A β as a critical early trigger in the chain of events that lead to tauopathy, neuronal dysfunction, and dementia 16, the degree of Tau deposition correlates with the cognitive decline in AD 17,18 questioning the role of Aβ deposition as the trigger for Tau pathogenesis.