What's That (Blue) Spot on my MRI? Multimodal Neuroimaging of the Locus Coeruleus in Neurodegenerative Disease

• Type of Material: Article
• Authors: Michael Kelberman, Emory University; Shella Keilholz, Emory University; David Weinshenker, Emory University
• Language: English
• Date: 2020-10-06
• Publisher: FRONTIERS MEDIA SA
• Publication Version: Final Published Version
• Copyright Statement: © 2020 Kelberman, Keilholz and Weinshenker.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3389/fnins.2020.583421
• Title of Journal or Parent Work: FRONTIERS IN NEUROSCIENCE
• Volume: 14
• Start Page: 583421
• End Page: 583421
• Grant/Funding Information: This work was supported by the National Institute of Aging (AG062581 to DW and SK, AG061175 to DW, and AG069502 to MK) and the National Institute of Neurological Disorders and Stroke (NS078095 to SK and NS096050 to MK).
• Keywords: EARLY-STAGE; Science & Technology; Life Sciences & Biomedicine; TAU PATHOLOGY; Neurosciences; PARKINSONS-DISEASE; EMISSION-TOMOGRAPHY TRACER; Parkinson's disease; Alzheimer's disease; STATE FUNCTIONAL CONNECTIVITY; NONHUMAN PRIMATE MODELS; NORADRENERGIC SYSTEM; locus coeruleus; Neurosciences & Neurology; ALZHEIMERS-DISEASE; positron emission tomography; neurodegeneration; animal models; IN-VIVO; SUBSTANTIA-NIGRA; magnetic resonance imaging
• Research Categories: Health Sciences, Radiology; Biology, Neuroscience

Abstract

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.