APP and Alzheimer disease: The neurovascular degeneration hypothesis of AD postulates that neurovascular dysfunction can lead to the onset or worsening of AD dementia through factors such as blood-brain barrier dysfunction and impaired cerebral blood flow (CBF), which can result in the development of tau-related pathology and a build-up of amyloid-beta peptide (Aβ),4,5 considered to be neuropathological hallmarks of AD.6