Numerical Simulations Reveal Complementary Function of Blood-Brain Barrier and Glymphatic Transport in the Brain

The brain accounts for approximately 20% of metabolism and, as a result, generates protein waste which requires efficient clearance. Failure to clear such waste leads to formation of toxic protein aggregates implicated in a variety of neurodegenerative diseases, including Alzheimer's and Parkinson's. The blood-brain barrier and the glymphatic system are two parallel transport pathways that remove waste from the brain, but very few studies have investigated their interactions or complementary function. Herein, we develop a Lattice Boltzmann simulation of waste clearance from an idealized segment of brain tissue and test the effects of selectively activating or deactivating each pathway. We model clearance of the peptide amyloid-β, long recognized as critical in Alzheimer's pathology, and calibrate our model against limited experimental data. This approach uncovers critical parameters that have eluded prior experimental measurement. Our study also reveals complementary functionality of the blood-brain barrier and glymphatic system that are likely generic features applicable to the transport of large molecules (e.g., proteins) in the brain.