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Amyloid‐β efflux from the central nervous system into the plasma
Author(s) -
Roberts Kaleigh Filisa,
Elbert Donald L.,
Kasten Tom P.,
Patterson Bruce W.,
Sigurdson Wendy C.,
Connors Rose E.,
Ovod Vitaliy,
Munsell Ling Y.,
Mawuenyega Kwasi G.,
MillerThomas Michelle M.,
Moran Christopher J.,
Cross Dewitte T.,
Derdeyn Colin P.,
Bateman Randall J.
Publication year - 2014
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.24270
Subject(s) - cerebrospinal fluid , medicine , venous blood , central nervous system , internal jugular vein , arterial blood , peripheral , blood–brain barrier , vein , anesthesia , femoral vein , jugular vein , cardiology , surgery
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 Aβ 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, Aβ concentration was assessed by 3 assays, and the venous to arterial Aβ concentration ratios were determined. Results Aβ 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 Aβ concentration compared to arterial blood concentration. Interpretation Our results are consistent with clearance of CNS‐derived Aβ into the venous blood supply with no increase from a peripheral capillary bed. Modeling these results suggests that direct transport of Aβ across the blood–brain barrier accounts for ∼25% of Aβ clearance, and reabsorption of cerebrospinal fluid Aβ accounts for ∼25% of the total CNS Aβ clearance in humans. Ann Neurol 2014;76:837–844