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advection, Alzheimer’s disease, amyloid, beta blockers, biophysics, glymphatic system, bulk flow, cerebrospinal fluid, circulation, hydraulic, interstitial, intracranial pressure, perivascular, pia mater, pulsation, subarachnoid space, Virchow-Robin space, waste disposal


This study exercises a new mathematical model to search for unappreciated therapeutic targets in Alzheimer’s disease. The model describes detailed mechanisms underlying the glymphatic pump mechanism, which removes toxic proteins of Alzheimer’s disease from the interstitial fluid of the brain. It shows that the glymphatic pump is driven by the amplitude of intracranial pressure pulsations in the subarachnoid space, which are correlated with the arterial pulse and modulated by many other factors. Implementing ways to increase intracranial pressure pulses quickly comes to mind as a potential treatment strategy. Specific interventions include drugs that increase arterial pulse volume and small devices similar to balloon pumps to create increased subarachnoid pressure pulsations. Computer simulations of such balloon-like pumps, expanding and contracting in synchrony with the heartbeat, show effective enhancement of subarachnoid space pressure pulsations and resulting interstitial fluid flow in the brain. Design concepts for both totally implanted and externally wearable pumps are presented.