Beta-amyloid accumulation within arterial walls in cerebral amyloid angiopathy is associated with the onset of Alzheimer's disease. However, the mechanism of beta-amyloid clearance along peri-arterial pathways in the brain is not well understood. In this study, we investigate a transport mechanism in the arterial basement membrane consisting of forward-propagating waves and their reflections. The arterial basement membrane is modeled as a periodically deforming annulus filled with an incompressible single-phase Newtonian fluid. A reverse flow, which has been suggested in literature as a beta-amyloid clearance pathway, can be induced by the motion of reflected boundary waves along the annular walls. The wave amplitude and the volume of the annular region govern the flow magnitude and may have important implications for an aging brain. Magnitudes of transport obtained from control volume analysis and numerical solutions of the Navier-Stokes equations are presented.

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The failure to clear amyloid-Beta from an aging brain leads to its accumulation within the walls of arteries and potentially to Alzheimer's disease. However, the clearance mechanism through the intramural periarterial pathway is not well understood. We previously proposed a hydrodynamic reverse transport model for the cerebral arterial basement membrane pathway. In our model, solute transport results from fluidic forcing driven by the superposition of forward and reverse propagating boundary waves. The aim of this study is to experimentally validate this hydrodynamic reverse transport mechanism in a microfluidic device where reverse transport in a rectangular conduit is driven by applying waveforms along its boundaries. Our results support our theory that while the superimposed boundary waves propagate in the forward direction, a reverse flow in the rectangular conduit can be induced by boundary wave reflections. We quantified the fluid transport velocity and direction under various boundary conditions and analyzed numerical simulations that support our experimental findings. We identified a set of boundary wave parameters that achieved reverse transport, which could be responsible for intramural periarterial drainage of cerebral metabolic waste.

We report on a computational model used to study the reversal of flow direction inside the annular region between concentric micro-cylinders filled with an incompressible Newtonian fluid. The flow is induced by boundary deformations on the inner and outer cylinder surfaces due to forward-propagating transverse waves and their reflections. This microfluidic transport mechanism is postulated as a vital pathway for removal of beta-amyloid from the brain along sub-millimeter cerebral arteries, and failure of this clearance is associated with Alzheimer’s disease. We show that the direction of this annular flow depends on superposition of the peristaltic waves and their reflection waves. A control volume analysis is developed to predict the transport characteristics and compared with numerical solutions of the Navier-Stokes equations. The identified set of microfluidic parameters that leads to a net reverse flow will aid biologists in understanding why an aging brain becomes prone to beta-amyloid accumulation.