What’s That (Blue) Spot on my MRI? Multimodal Neuroimaging of the Locus Coeruleus in Neurodegenerative Disease
The locus coeruleus (LC) has long been underappreciated for its role in the pathophysiology of Alzheimer’s disease (AD), Parkinson’s disease (PD), and other neurodegenerative disorders. While AD and PD are distinct in clinical presentation, both are characterized by prodromal protein aggregation in...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-10-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnins.2020.583421/full |
| _version_ | 1819315786611687424 |
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| author | Michael Kelberman Shella Keilholz David Weinshenker |
| author_facet | Michael Kelberman Shella Keilholz David Weinshenker |
| author_sort | Michael Kelberman |
| collection | DOAJ |
| description | The locus coeruleus (LC) has long been underappreciated for its role in the pathophysiology of Alzheimer’s disease (AD), Parkinson’s disease (PD), and other neurodegenerative disorders. While AD and PD are distinct in clinical presentation, both are characterized by prodromal protein aggregation in the LC, late-stage degeneration of the LC, and comorbid conditions indicative of LC dysfunction. Many of these early studies were limited to post-mortem histological techniques due to the LC’s small size and location deep in the brainstem. Thus, there is a growing interest in utilizing in vivo imaging of the LC as a predictor of preclinical neurodegenerative processes and biomarker of disease progression. Simultaneously, neuroimaging in animal models of neurodegenerative disease holds promise for identifying early alterations to LC circuits, but has thus far been underutilized. While still in its infancy, a handful of studies have reported effects of single gene mutations and pathology on LC function in disease using various neuroimaging techniques. Furthermore, combining imaging and optogenetics or chemogenetics allows for interrogation of network connectivity in response to changes in LC activity. The purpose of this article is twofold: (1) to review what magnetic resonance imaging (MRI) and positron emission tomography (PET) have revealed about LC dysfunction in neurodegenerative disease and its potential as a biomarker in humans, and (2) to explore how animal models can be used to test hypotheses derived from clinical data and establish a mechanistic framework to inform LC-focused therapeutic interventions to alleviate symptoms and impede disease progression. |
| first_indexed | 2024-12-24T10:05:39Z |
| format | Article |
| id | doaj.art-327e828bcce1458ba377f4c062aa88e2 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-24T10:05:39Z |
| publishDate | 2020-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-327e828bcce1458ba377f4c062aa88e22022-12-21T17:00:50ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2020-10-011410.3389/fnins.2020.583421583421What’s That (Blue) Spot on my MRI? Multimodal Neuroimaging of the Locus Coeruleus in Neurodegenerative DiseaseMichael Kelberman0Shella Keilholz1David Weinshenker2Department of Human Genetics, Emory University, Atlanta, GA, United StatesThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Emory University, Atlanta, GA, United StatesDepartment of Human Genetics, Emory University, Atlanta, GA, United StatesThe locus coeruleus (LC) has long been underappreciated for its role in the pathophysiology of Alzheimer’s disease (AD), Parkinson’s disease (PD), and other neurodegenerative disorders. While AD and PD are distinct in clinical presentation, both are characterized by prodromal protein aggregation in the LC, late-stage degeneration of the LC, and comorbid conditions indicative of LC dysfunction. Many of these early studies were limited to post-mortem histological techniques due to the LC’s small size and location deep in the brainstem. Thus, there is a growing interest in utilizing in vivo imaging of the LC as a predictor of preclinical neurodegenerative processes and biomarker of disease progression. Simultaneously, neuroimaging in animal models of neurodegenerative disease holds promise for identifying early alterations to LC circuits, but has thus far been underutilized. While still in its infancy, a handful of studies have reported effects of single gene mutations and pathology on LC function in disease using various neuroimaging techniques. Furthermore, combining imaging and optogenetics or chemogenetics allows for interrogation of network connectivity in response to changes in LC activity. The purpose of this article is twofold: (1) to review what magnetic resonance imaging (MRI) and positron emission tomography (PET) have revealed about LC dysfunction in neurodegenerative disease and its potential as a biomarker in humans, and (2) to explore how animal models can be used to test hypotheses derived from clinical data and establish a mechanistic framework to inform LC-focused therapeutic interventions to alleviate symptoms and impede disease progression.https://www.frontiersin.org/article/10.3389/fnins.2020.583421/fulllocus coeruleusneurodegenerationAlzheimer’s diseaseParkinson’s diseasemagnetic resonance imagingpositron emission tomography |
| spellingShingle | Michael Kelberman Shella Keilholz David Weinshenker What’s That (Blue) Spot on my MRI? Multimodal Neuroimaging of the Locus Coeruleus in Neurodegenerative Disease Frontiers in Neuroscience locus coeruleus neurodegeneration Alzheimer’s disease Parkinson’s disease magnetic resonance imaging positron emission tomography |
| title | What’s That (Blue) Spot on my MRI? Multimodal Neuroimaging of the Locus Coeruleus in Neurodegenerative Disease |
| title_full | What’s That (Blue) Spot on my MRI? Multimodal Neuroimaging of the Locus Coeruleus in Neurodegenerative Disease |
| title_fullStr | What’s That (Blue) Spot on my MRI? Multimodal Neuroimaging of the Locus Coeruleus in Neurodegenerative Disease |
| title_full_unstemmed | What’s That (Blue) Spot on my MRI? Multimodal Neuroimaging of the Locus Coeruleus in Neurodegenerative Disease |
| title_short | What’s That (Blue) Spot on my MRI? Multimodal Neuroimaging of the Locus Coeruleus in Neurodegenerative Disease |
| title_sort | what s that blue spot on my mri multimodal neuroimaging of the locus coeruleus in neurodegenerative disease |
| topic | locus coeruleus neurodegeneration Alzheimer’s disease Parkinson’s disease magnetic resonance imaging positron emission tomography |
| url | https://www.frontiersin.org/article/10.3389/fnins.2020.583421/full |
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