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Regulation of amyloid-β dynamics and pathology by the circadian clock

Nighttime restlessness and daytime drowsiness are common and early symptoms of Alzheimer’s Disease (AD). This symptomology implicates dysfunctional biological timing, yet the role of the circadian system in AD pathogenesis is unknown. To evaluate the role of the circadian clock in amyloid-β (Aβ) dyn...

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Autores principales: Kress, Geraldine J., Liao, Fan, Dimitry, Julie, Cedeno, Michelle R., FitzGerald, Garret A., Holtzman, David M., Musiek, Erik S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881473/
https://www.ncbi.nlm.nih.gov/pubmed/29382695
http://dx.doi.org/10.1084/jem.20172347
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author Kress, Geraldine J.
Liao, Fan
Dimitry, Julie
Cedeno, Michelle R.
FitzGerald, Garret A.
Holtzman, David M.
Musiek, Erik S.
author_facet Kress, Geraldine J.
Liao, Fan
Dimitry, Julie
Cedeno, Michelle R.
FitzGerald, Garret A.
Holtzman, David M.
Musiek, Erik S.
author_sort Kress, Geraldine J.
collection PubMed
description Nighttime restlessness and daytime drowsiness are common and early symptoms of Alzheimer’s Disease (AD). This symptomology implicates dysfunctional biological timing, yet the role of the circadian system in AD pathogenesis is unknown. To evaluate the role of the circadian clock in amyloid-β (Aβ) dynamics and pathology, we used a mouse model of β-amyloidosis and disrupted circadian clock function either globally or locally in the brain via targeted deletion of the core clock gene Bmal1. Our results demonstrate that loss of central circadian rhythms leads to disruption of daily hippocampal interstitial fluid Aβ oscillations and accelerates amyloid plaque accumulation, whereas loss of peripheral Bmal1 in the brain parenchyma increases expression of Apoe and promotes fibrillar plaque deposition. These results provide evidence that both central circadian rhythms and local clock function influence Aβ dynamics and plaque formation and demonstrate mechanisms by which poor circadian hygiene may directly influence AD pathogenesis.
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spelling pubmed-58814732018-10-02 Regulation of amyloid-β dynamics and pathology by the circadian clock Kress, Geraldine J. Liao, Fan Dimitry, Julie Cedeno, Michelle R. FitzGerald, Garret A. Holtzman, David M. Musiek, Erik S. J Exp Med Research Articles Nighttime restlessness and daytime drowsiness are common and early symptoms of Alzheimer’s Disease (AD). This symptomology implicates dysfunctional biological timing, yet the role of the circadian system in AD pathogenesis is unknown. To evaluate the role of the circadian clock in amyloid-β (Aβ) dynamics and pathology, we used a mouse model of β-amyloidosis and disrupted circadian clock function either globally or locally in the brain via targeted deletion of the core clock gene Bmal1. Our results demonstrate that loss of central circadian rhythms leads to disruption of daily hippocampal interstitial fluid Aβ oscillations and accelerates amyloid plaque accumulation, whereas loss of peripheral Bmal1 in the brain parenchyma increases expression of Apoe and promotes fibrillar plaque deposition. These results provide evidence that both central circadian rhythms and local clock function influence Aβ dynamics and plaque formation and demonstrate mechanisms by which poor circadian hygiene may directly influence AD pathogenesis. Rockefeller University Press 2018-04-02 /pmc/articles/PMC5881473/ /pubmed/29382695 http://dx.doi.org/10.1084/jem.20172347 Text en © 2018 Kress et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/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 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Kress, Geraldine J.
Liao, Fan
Dimitry, Julie
Cedeno, Michelle R.
FitzGerald, Garret A.
Holtzman, David M.
Musiek, Erik S.
Regulation of amyloid-β dynamics and pathology by the circadian clock
title Regulation of amyloid-β dynamics and pathology by the circadian clock
title_full Regulation of amyloid-β dynamics and pathology by the circadian clock
title_fullStr Regulation of amyloid-β dynamics and pathology by the circadian clock
title_full_unstemmed Regulation of amyloid-β dynamics and pathology by the circadian clock
title_short Regulation of amyloid-β dynamics and pathology by the circadian clock
title_sort regulation of amyloid-β dynamics and pathology by the circadian clock
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881473/
https://www.ncbi.nlm.nih.gov/pubmed/29382695
http://dx.doi.org/10.1084/jem.20172347
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