Fig.2.

Vascular changes may influence Alzheimer’s disease lesion burden. A) Scheme and arrows indicate how cerebrovascular factors affect amyloid-β (Aβ) processing and clearance. (1) Hypoperfusion, as a result of arteriolosclerosis or blood–brain barrier disruption, elevates BACE1 levels and activity, leading to Aβ overproduction. (2) Aβ overproduction leads to amyloid plaque formation and cerebral amyloid angiopathy (CAA); CAA impairs Aβ clearance efficiency, thus forming a cycle of Aβ clearance failure. (3) CAA further potentiates deficiencies of blood flow by aggravating preexisting arteriosclerosis and BBB disruption, thus forming a cycle of Aβ overproduction. AF can modify and drive such vicious cycles through concomitant hypoperfusion. B) AF may accelerate Alzheimer’s disease indirectly through cerebrovascular disease such as cardioembolic stroke and white matter changes. Note that arteriolosclerosis is known to be associated with ischemic stroke while CAA with white matter changes, which may further drive the vicious cycle of dementia.