Affiliations: [a] Geriatric Research, Education, and Clinical Center | [b] Veterans Affairs Puget Sound Health Care System | [c] Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, USA | [d] Department of Psychology, University of Washington, Seattle, WA, USA | [e] Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA | [f] Department of Pharmacology, University of Washington School of Medicine, Seattle, WA, USA | [g] LKS Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong
Correspondence:
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Corresponding author: David G. Cook, Veterans Affairs Puget Sound Health Care System, 1660 South Columbian Way, Seattle, WA 98108, USA. Tel.: +1 206 786 5437; Fax: +1 206 764 2569; E-mail: dgcook@u.washington.edu.
Note: [1] These authors contributed equally to this work.
Note: [] Communicated by Thomas Montine
Abstract: Amyloid-β (Aβ) is cleared from the brain by both proteolytic digestion and transport across the blood-brain-barrier into the peripheral circulatory system. To investigate the role peripheral Aβ levels play in regulating Aβ brain clearance, we measured the clearance of [125I]-Aβ1–40 injected into the brains of liver-ligated rats that allowed peripheral Aβ levels to be maintained at elevated levels for approximately one hour with/without a single peripheral bolus of unlabeled Aβ1–40. We found that elevating peripheral Aβlevels significantly decreased [125]-Aβ1–40 brain clearance, thus supporting the hypothesis that peripheral Aβ levels regulate Aβ clearance from the central nervous system.
