APP and Alzheimer disease: According to the neurovascular hypothesis, among the causes of Aβ accumulation in the CNS, the absence or reduction of Aβ degradation, reduction of Aβ clearance, or increase of Aβ influx along the BBB is indicated.8Mechanisms leading to Aβ accumulation in AD are excessive Aβ production as a result of mutations in APP or genes, and impairment of clearance of Aβ due to changes in Aβ aggregation properties and/or Aβ removal processes.