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The Locus Coeruleus in Aging and Alzheimer's Disease: A post-mortem and brain imaging review

The Locus Coeruleus in Aging and Alzheimer's Disease: A post-mortem and brain imaging review
The Locus Coeruleus in Aging and Alzheimer's Disease: A post-mortem and brain imaging review
The locus coeruleus (LC), a tiny nucleus in the brainstem and the principle 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. Whilst 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 post-mortem, 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.
Locus coeruleus, aging, Alzheimer’s disease, magnetic resonance imaging, human, neuromelanin
1387-2877
5-22
Beardmore, Rebecca C
cf4540a1-d1b1-4208-b0f4-d647210e9a0d
Hou, Ruihua
470bdcbc-93a9-4dad-aac5-26d455c34376
Darekar, Angela
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Holmes, Clive
ada5abf3-8459-4cf7-be40-3f4e9391cc96
Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61
Beardmore, Rebecca C
cf4540a1-d1b1-4208-b0f4-d647210e9a0d
Hou, Ruihua
470bdcbc-93a9-4dad-aac5-26d455c34376
Darekar, Angela
f7b566e5-3568-4c27-aed9-a5275f7a5cf5
Holmes, Clive
ada5abf3-8459-4cf7-be40-3f4e9391cc96
Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61

Beardmore, Rebecca C, Hou, Ruihua, Darekar, Angela, Holmes, Clive and Boche, Delphine (2021) The Locus Coeruleus in Aging and Alzheimer's Disease: A post-mortem and brain imaging review. Journal of Alzheimer's Disease, 83 (1), 5-22, [21-0191R2]. (doi:10.3233/JAD-210191). (In Press)

Record type: Review

Abstract

The locus coeruleus (LC), a tiny nucleus in the brainstem and the principle 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. Whilst 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 post-mortem, 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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Revised_Locus_coeruleus_review_v2 - Accepted Manuscript
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Accepted/In Press date: 11 June 2021
Keywords: Locus coeruleus, aging, Alzheimer’s disease, magnetic resonance imaging, human, neuromelanin

Identifiers

Local EPrints ID: 449835
URI: http://eprints.soton.ac.uk/id/eprint/449835
ISSN: 1387-2877
PURE UUID: 4a42e86a-0ccf-4740-a3d4-5389d942e383
ORCID for Ruihua Hou: ORCID iD orcid.org/0000-0001-6127-1478
ORCID for Clive Holmes: ORCID iD orcid.org/0000-0003-1999-6912
ORCID for Delphine Boche: ORCID iD orcid.org/0000-0002-5884-130X

Catalogue record

Date deposited: 21 Jun 2021 16:31
Last modified: 22 Nov 2021 02:55

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Contributors

Author: Rebecca C Beardmore
Author: Ruihua Hou ORCID iD
Author: Angela Darekar
Author: Clive Holmes ORCID iD
Author: Delphine Boche ORCID iD

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