Modeling the Impact of Cerebrospinal Fluid Flow on Waste Clearance in the Brain

The flow of cerebrospinal fluid (CSF) through the brain parenchyma is partially responsible for the clearance of waste products such as beta-amyloid or tau protein, associated with Alzheimer's disease. Reduced flow can lead to accumulation of the harmful species. The predominant flow of CSF is from the ventricles to the recently rediscovered subarachnoid lymph vessels. The mechanics of CSF flow affect how well waste is cleared as well as the locations in which species accumulate. These mechanics have yet to be fully investigated. Experiments in human brains are difficult and costly, and generally rely on observational studies without control of flow parameters. Here, a computational model is used to simulate flow of CSF to improve understanding of the mechanisms involved in waste clearance. The finite element model was first developed in a spherical geometry for validation with a closed form solution. Following validation, a more detailed mesh was developed using MRI scans of human and rat brains. A variety of boundary, initial conditions, and physical parameters (e.g., diffusion coefficients, species production rates) were tested to examine conditions associated with healthy and diseased brains. Determining the parameters that have significant impact on the concentration distribution, as well as the magnitude required to create a change in the distribution, can provide insights in the pathogenesis of Alzheimer's disease, and guide design of subsequent in vitro and in vivo studies. These studies may provide guidance in the development of appropriate treatments.