In vivo measurements reveal cerebrospinal fluid flow reduction in hypertension

High blood pressure promotes deposition of amyloid-β and is a known risk factor for Alzheimer’s disease. The mechanisms underlying this interaction are not well understood. Removal of amyloid-β from the brain’s interstitial fluid is facilitated by the flow of cerebrospinal fluid (CSF) through perivascular spaces (PVSs) which surround the cerebral vasculature. However, limitations in imaging techniques have impeded the measurement of such flows. Recently, our interdisciplinary collaboration has developed a novel in vivo imaging approach combining two photon microscopy and particle tracking velocimetry which has enabled the first ever quantitative measurements of CSF flow in the PVSs of mouse brains. Our measurements support the hypothesis that such flows are driven primarily by motion of the adjacent arterial wall, a peristalsis-like effect previously referred to as perivascular pumping. By increasing blood pressure, we alter the dynamics of the arterial wall motion and observe a concurrent decrease in the net CSF flow speed. Our results offer a potential causal mechanism by which hypertension reduces perivascular pumping of CSF leading to increased risk for neurodegenerative disorders, including Alzheimer's disease.