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The Locus Coeruleus in Aging and Alzheimer’s Disease: A Postmortem and Brain Imaging Review

The locus coeruleus (LC), a tiny nucleus in the brainstem and the principal site of noradrenaline synthesis, has a major role in regulating autonomic function, arousal, attention, and neuroinflammation. LC dysfunction has been linked to a range of disorders; however particular interest is given to t...

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Autores principales: Beardmore, Rebecca, Hou, Ruihua, Darekar, Angela, Holmes, Clive, Boche, Delphine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: IOS Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461706/
https://www.ncbi.nlm.nih.gov/pubmed/34219717
http://dx.doi.org/10.3233/JAD-210191
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author Beardmore, Rebecca
Hou, Ruihua
Darekar, Angela
Holmes, Clive
Boche, Delphine
author_facet Beardmore, Rebecca
Hou, Ruihua
Darekar, Angela
Holmes, Clive
Boche, Delphine
author_sort Beardmore, Rebecca
collection PubMed
description The locus coeruleus (LC), a tiny nucleus in the brainstem and the principal site of noradrenaline synthesis, has a major role in regulating autonomic function, arousal, attention, and neuroinflammation. LC dysfunction has been linked to a range of disorders; however particular interest is given to the role it plays in Alzheimer’s disease (AD). The LC undergoes significant neuronal loss in AD, thought to occur early in the disease process. While neuronal loss in the LC has also been suggested to occur in aging, this relationship is less clear as the findings have been contradictory. LC density has been suggested to be indicative of cognitive reserve and the evidence for these claims will be discussed. Recent imaging techniques allowing visualization of the LC in vivo using neuromelanin-sensitive MRI are developing our understanding of the role of LC in aging and AD. Tau pathology within the LC is evident at an early age in most individuals; however, the relationship between tau accumulation and neuronal loss and why some individuals then develop AD is not understood. Neuromelanin pigment accumulates within LC cells with age and is proposed to be toxic and inflammatory when released into the extracellular environment. This review will explore our current knowledge of the LC changes in both aging and AD from postmortem, imaging, and experimental studies. We will discuss the reasons behind the susceptibility of the LC to neuronal loss, with a focus on the role of extracellular neuromelanin and neuroinflammation caused by the dysfunction of the LC-noradrenaline pathway.
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spelling pubmed-84617062021-10-08 The Locus Coeruleus in Aging and Alzheimer’s Disease: A Postmortem and Brain Imaging Review Beardmore, Rebecca Hou, Ruihua Darekar, Angela Holmes, Clive Boche, Delphine J Alzheimers Dis Review The locus coeruleus (LC), a tiny nucleus in the brainstem and the principal site of noradrenaline synthesis, has a major role in regulating autonomic function, arousal, attention, and neuroinflammation. LC dysfunction has been linked to a range of disorders; however particular interest is given to the role it plays in Alzheimer’s disease (AD). The LC undergoes significant neuronal loss in AD, thought to occur early in the disease process. While neuronal loss in the LC has also been suggested to occur in aging, this relationship is less clear as the findings have been contradictory. LC density has been suggested to be indicative of cognitive reserve and the evidence for these claims will be discussed. Recent imaging techniques allowing visualization of the LC in vivo using neuromelanin-sensitive MRI are developing our understanding of the role of LC in aging and AD. Tau pathology within the LC is evident at an early age in most individuals; however, the relationship between tau accumulation and neuronal loss and why some individuals then develop AD is not understood. Neuromelanin pigment accumulates within LC cells with age and is proposed to be toxic and inflammatory when released into the extracellular environment. This review will explore our current knowledge of the LC changes in both aging and AD from postmortem, imaging, and experimental studies. We will discuss the reasons behind the susceptibility of the LC to neuronal loss, with a focus on the role of extracellular neuromelanin and neuroinflammation caused by the dysfunction of the LC-noradrenaline pathway. IOS Press 2021-08-31 /pmc/articles/PMC8461706/ /pubmed/34219717 http://dx.doi.org/10.3233/JAD-210191 Text en © 2021 – The authors. Published by IOS Press https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Beardmore, Rebecca
Hou, Ruihua
Darekar, Angela
Holmes, Clive
Boche, Delphine
The Locus Coeruleus in Aging and Alzheimer’s Disease: A Postmortem and Brain Imaging Review
title The Locus Coeruleus in Aging and Alzheimer’s Disease: A Postmortem and Brain Imaging Review
title_full The Locus Coeruleus in Aging and Alzheimer’s Disease: A Postmortem and Brain Imaging Review
title_fullStr The Locus Coeruleus in Aging and Alzheimer’s Disease: A Postmortem and Brain Imaging Review
title_full_unstemmed The Locus Coeruleus in Aging and Alzheimer’s Disease: A Postmortem and Brain Imaging Review
title_short The Locus Coeruleus in Aging and Alzheimer’s Disease: A Postmortem and Brain Imaging Review
title_sort locus coeruleus in aging and alzheimer’s disease: a postmortem and brain imaging review
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461706/
https://www.ncbi.nlm.nih.gov/pubmed/34219717
http://dx.doi.org/10.3233/JAD-210191
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