Amyloid-β Efflux from the Central Nervous System into the Plasma

ObjectiveThe aim of this study was to measure the flux of amyloid- (A) across the human cerebral capillary bed to determine whether transport into the blood is a significant mechanism of clearance for A produced in the central nervous system (CNS). MethodsTime-matched blood samples were simultaneously collected from a cerebral vein (including the sigmoid sinus, inferior petrosal sinus, and the internal jugular vein), femoral vein, and radial artery of patients undergoing inferior petrosal sinus sampling. For each plasma sample, A concentration was assessed by 3 assays, and the venous to arterial A concentration ratios were determined. ResultsA concentration was increased by approximate to 7.5% in venous blood leaving the CNS capillary bed compared to arterial blood, indicating efflux from the CNS into the peripheral blood (p<0.0001). There was no difference in peripheral venous A concentration compared to arterial blood concentration. InterpretationOur results are consistent with clearance of CNS-derived A into the venous blood supply with no increase from a peripheral capillary bed. Modeling these results suggests that direct transport of A across the blood-brain barrier accounts for approximate to 25% of A clearance, and reabsorption of cerebrospinal fluid A accounts for approximate to 25% of the total CNS A clearance in humans. Ann Neurol 2014;76:837-844