Perivascular brain clearance as a therapeutic target in cerebral amyloid angiopathy and Alzheimer's disease

Abstract

Although distinct diseases, both cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD) are characterized by the aggregation and accumulation of amyloid-β (Aβ). This is thought to be due, in part, to impaired perivascular Aβ clearance from the brain. This shared failure in both diseases presents a common opportunity for therapeutic intervention. In this review we discuss the idea that promoting perivascular brain clearance could be an effective strategy for safely reducing Aβ levels in CAA and AD thereby improving clinical outcomes, most notably hemorrhagic stroke and cognitive decline. We will explore the evidence for the different forces that are thought to drive perivascular brain clearance, review the literature on potential strategies for potentiating these driving forces, and finally we will discuss the substantial translational challenges and considerations that would accompany such an intervention.

Keywords: Cerebral amyloid angiopathy; Glymphatic system; Intramural periarterial drainage; Mixing; Vascular smooth muscle cells.