ACE and hypertensive disorder: The proposals include a theory of homeostasis disruption whereby increased levels of ACE mediate short-term Aβ clearance but that up-regulation of Ang II in turn causes hypertension, damage to the blood–brain barrier, reduced cerebral blood flow results in de novo Aβ deposition, inflammation, regional white matter volume changes, and reduced cholinergic activity [35, 42–44].