In vivo measurements reveal alteration of vessel pulsations and cerebrospinal fluid flow with age*

In the body, cellular waste is cleared via the lymphatic system; however, this system does not extend to the brain even though it consumes 20% of total metabolism and generates its own weight in waste annually. Failure to remove metabolic wastes, such as amyloid-β, leads to formation of plaques that disrupt neuronal function, culminating in Alzheimer’s disease. One mechanism for brain waste removal is bulk flow of cerebrospinal fluid (CSF) via perivascular spaces (annular channels that line cerebral vasculature). This pathway is known as the glymphatic system. Despite rapidly growing research interest, mechanisms driving CSF flow are poorly understood. One proposed driving mechanism is arterial pulsations linked to the cardiac cycle. Changes in the compliance of vasculature due to heart disease and/or aging could thus play a significant role in impaired glymphatic flow leading to development of neurodegenerative diseases. We present in vivo measurements of CSF transport by injecting and then tracking fluorescent microspheres flowing at the surface of the brain in young and old mice to quantify changes in arterial wall compliance and flow speed. Our preliminary measurements support a causal mechanism linking decline in cardiovascular health to pathology of neurodegenerative diseases.