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Rapid in vivo measurement of β-amyloid reveals biphasic clearance kinetics in an Alzheimer’s mouse model

Findings from genetic, animal model, and human studies support the observation that accumulation of the β-amyloid (Aβ) peptide in the brain plays a central role in the pathogenic cascade of Alzheimer’s disease (AD). Human studies suggest that one key factor leading to accumulation is a defect in bra...

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Autores principales: Yuede, Carla M., Lee, Hyo, Restivo, Jessica L., Davis, Todd A., Hettinger, Jane C., Wallace, Clare E., Young, Katherine L., Hayne, Margaret R., Bu, Guojun, Li, Chen-zhong, Cirrito, John R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4854730/
https://www.ncbi.nlm.nih.gov/pubmed/27069115
http://dx.doi.org/10.1084/jem.20151428
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author Yuede, Carla M.
Lee, Hyo
Restivo, Jessica L.
Davis, Todd A.
Hettinger, Jane C.
Wallace, Clare E.
Young, Katherine L.
Hayne, Margaret R.
Bu, Guojun
Li, Chen-zhong
Cirrito, John R.
author_facet Yuede, Carla M.
Lee, Hyo
Restivo, Jessica L.
Davis, Todd A.
Hettinger, Jane C.
Wallace, Clare E.
Young, Katherine L.
Hayne, Margaret R.
Bu, Guojun
Li, Chen-zhong
Cirrito, John R.
author_sort Yuede, Carla M.
collection PubMed
description Findings from genetic, animal model, and human studies support the observation that accumulation of the β-amyloid (Aβ) peptide in the brain plays a central role in the pathogenic cascade of Alzheimer’s disease (AD). Human studies suggest that one key factor leading to accumulation is a defect in brain Aβ clearance. We have developed a novel microimmunoelectrode (MIE) to study the kinetics of Aβ clearance using an electrochemical approach. This is the first study using MIEs in vivo to measure rapid changes in Aβ levels in the brains of living mice. Extracellular, interstitial fluid (ISF) Aβ levels were measured in the hippocampus of APP/PS1 mice. Baseline levels of Aβ(40) in the ISF are relatively stable and begin to decline within minutes of blocking Aβ production with a γ-secretase inhibitor. Pretreatment with a P-glycoprotein inhibitor, which blocks blood–brain barrier transport of Aβ, resulted in significant prolongation of Aβ(40) half-life, but only in the latter phase of Aβ clearance from the ISF.
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spelling pubmed-48547302016-11-02 Rapid in vivo measurement of β-amyloid reveals biphasic clearance kinetics in an Alzheimer’s mouse model Yuede, Carla M. Lee, Hyo Restivo, Jessica L. Davis, Todd A. Hettinger, Jane C. Wallace, Clare E. Young, Katherine L. Hayne, Margaret R. Bu, Guojun Li, Chen-zhong Cirrito, John R. J Exp Med Research Articles Findings from genetic, animal model, and human studies support the observation that accumulation of the β-amyloid (Aβ) peptide in the brain plays a central role in the pathogenic cascade of Alzheimer’s disease (AD). Human studies suggest that one key factor leading to accumulation is a defect in brain Aβ clearance. We have developed a novel microimmunoelectrode (MIE) to study the kinetics of Aβ clearance using an electrochemical approach. This is the first study using MIEs in vivo to measure rapid changes in Aβ levels in the brains of living mice. Extracellular, interstitial fluid (ISF) Aβ levels were measured in the hippocampus of APP/PS1 mice. Baseline levels of Aβ(40) in the ISF are relatively stable and begin to decline within minutes of blocking Aβ production with a γ-secretase inhibitor. Pretreatment with a P-glycoprotein inhibitor, which blocks blood–brain barrier transport of Aβ, resulted in significant prolongation of Aβ(40) half-life, but only in the latter phase of Aβ clearance from the ISF. The Rockefeller University Press 2016-05-02 /pmc/articles/PMC4854730/ /pubmed/27069115 http://dx.doi.org/10.1084/jem.20151428 Text en © 2016 Yuede et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Yuede, Carla M.
Lee, Hyo
Restivo, Jessica L.
Davis, Todd A.
Hettinger, Jane C.
Wallace, Clare E.
Young, Katherine L.
Hayne, Margaret R.
Bu, Guojun
Li, Chen-zhong
Cirrito, John R.
Rapid in vivo measurement of β-amyloid reveals biphasic clearance kinetics in an Alzheimer’s mouse model
title Rapid in vivo measurement of β-amyloid reveals biphasic clearance kinetics in an Alzheimer’s mouse model
title_full Rapid in vivo measurement of β-amyloid reveals biphasic clearance kinetics in an Alzheimer’s mouse model
title_fullStr Rapid in vivo measurement of β-amyloid reveals biphasic clearance kinetics in an Alzheimer’s mouse model
title_full_unstemmed Rapid in vivo measurement of β-amyloid reveals biphasic clearance kinetics in an Alzheimer’s mouse model
title_short Rapid in vivo measurement of β-amyloid reveals biphasic clearance kinetics in an Alzheimer’s mouse model
title_sort rapid in vivo measurement of β-amyloid reveals biphasic clearance kinetics in an alzheimer’s mouse model
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4854730/
https://www.ncbi.nlm.nih.gov/pubmed/27069115
http://dx.doi.org/10.1084/jem.20151428
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