Fig. 7

Pathological changes in the vasculature and perivascular clearance in Alzheimer’s disease with CAA: Schematic summary. Cerebrospinal fluid (CSF) influx (blue arrow) and intramural periarterial drainage (IPAD) efflux (red arrow) occurring along the perivascular basement membrane (BM) under the influence of vascular pulsation in the healthy young brain (left). Astrocytes surround the perivascular BM to form glia limitans. Amyloid accumulation in the vascular wall leads to structural changes in the BM, loss of vascular smooth muscle cells (vSMCs), and augmented vascular pulsation in the Alzheimer’s disease brain (right). This vascular dysfunction inhibits perivascular CSF influx and IPAD efflux, and the pathological changes in the vasculature and clearance further worsen with the progression of CAA. The astrocytes located around the blood vessels and pia mater move around the parenchymal Aβ plaque, thus the glia limitans is also compromised