Amyloid-β efflux from the central nervous system into the plasma

Abstract

Objective: The aim of this study was to measure the flux of amyloid-β (Aβ) across the human cerebral capillary bed to determine whether transport into the blood is a significant mechanism of clearance for Ab produced in the central nervous system (CNS). Methods: Time-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, Ab concentration was assessed by 3 assays, and the venous to arterial A β concentration ratios were determined. Results: A β concentration was increased by ∼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 Ab concentration compared to arterial blood concentration. Interpretation: Our results are consistent with clearance of CNS-derived A β into the venous blood supply with no increase from a peripheral capillary bed. Modeling these results suggests that direct transport of Ab across theblood-brain barrier accounts for ∼25% of Aβ clearance, and reabsorption of cerebrospinal fluid Ab accounts for ∼25% of the total CNS Aβ clearance in humans.