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Front. Aging Neurosci. | doi: 10.3389/fnagi.2018.00127

Noradrenergic Dysfunction in Alzheimer’s and Parkinson’s Diseases – An Overview of Imaging Studies

  • 1Frank H. Netter MD School of Medicine, Quinnipiac University, United States
  • 2Psychiatry, Yale University, United States

Noradrenergic dysfunction contributes to cognitive impairment in Alzheimer’s Disease (AD) and Parkinson’s Disease (PD). Conventional therapeutic strategies seek to enhance cholinergic and dopaminergic neurotransmission in AD and PD, respectively, and few studies have examined noradrenergic dysfunction as a target for medication development. We review the literature of noradrenergic dysfunction in AD and PD with a focus on human imaging studies that implicate the locus coeruleus (LC) circuit. The LC sends noradrenergic projections diffusely throughout the cerebral cortex and plays a critical role in attention, learning, working memory and cognitive control. The LC undergoes considerable degeneration in both AD and PD. Advances in magnetic resonance imaging have facilitated greater understanding of how structural and functional alteration of the LC may contribute to cognitive decline in AD and PD. We discuss the potential roles of the noradrenergic system in the pathogenesis of AD and PD with an emphasis on postmortem anatomical studies, structural MRI studies, and functional MRI studies, where we highlight changes in LC connectivity with the default mode network (DMN). LC degeneration may accompany deficient capacity in suppressing DMN activity and increasing saliency and task control network activities to meet behavioral challenges. We finish by proposing potential and new directions of research to address noradrenergic dysfunction in AD and PD.

Keywords: Norepinephrine, Dopamine, neurodegeneration, neurodegenerative, Alzheimer, Parkinson, Locus Coeruleus, Ventral Tegmental Area, midbrain, MRI

Received: 21 Dec 2017; Accepted: 16 Apr 2018.

Edited by:

Fernanda Laezza, University of Texas Medical Branch, United States

Reviewed by:

Yoland Smith, Emory University, United States
Richard Camicioli, University of Alberta, Canada  

Copyright: © 2018 Peterson and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Chiang-Shan R. Li, Yale University, Psychiatry, Connecticut Mental Health Center S112, 34 Park Street, New Haven, 06519, Connecticut, United States, chiang-shan.li@yale.edu