Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Jan 1:1702:12-16.
doi: 10.1016/j.brainres.2018.01.001. Epub 2018 Jan 4.

Complex noradrenergic dysfunction in Alzheimer's disease: Low norepinephrine input is not always to blame

Mary Gannon  1 , Qin Wang  2
Affiliations

Complex noradrenergic dysfunction in Alzheimer's disease: Low norepinephrine input is not always to blame

Mary Gannon et al. Brain Res. .

Abstract

The locus coeruleus-noradrenergic (LC-NA) system supplies the cerebral cortex with norepinephrine, a key modulator of cognition. Neurodegeneration of the LC is an early hallmark of Alzheimer's disease (AD). In this article, we analyze current literature to understand whether NA degeneration in AD simply leads to a loss of norepinephrine input to the cortex. With reported adaptive changes in the LC-NA system at the anatomical, cellular, and molecular levels in AD, existing evidence support a seemingly sustained level of extracellular NE in the cortex, at least at early stages of the long course of AD. We postulate that loss of the integrity of the NA system, rather than mere loss of NE input, is a key contributor to AD pathogenesis. A thorough understanding of NA dysfunction in AD has a large impact on both our comprehension and treatment of this devastating disease.

Keywords: Alzheimer’s disease; Dysfunction; Locus coeruleus; Noradrenergic; Norepinephrine.

PubMed Disclaimer

References

    1. Abercrombie ED, Zigmond MJ, 1989. Partial injury to central noradrenergic neurons: reduction of tissue norepinephrine content is greater than reduction of extracellular norepinephrine measured by microdialysis. J. Neurosci 9, 4062–4067. - PMC - PubMed
    1. Adolfsson R et al. , 1979. Changes in the brain catecholamines in patients with dementia of Alzheimer type. Br. J. Psychiatry 135, 216–223. - PubMed
    1. Arnsten AF, Jentsch JD, 1997. The alpha-1 adrenergic agonist, cirazoline, impairs spatial working memory performance in aged monkeys. Pharmacol. Biochem. Behav 58, 55–59. - PubMed
    1. Arnsten AF, 1998. The biology of being frazzled. Science 280, 1711–1712. - PubMed
    1. Arnsten AF, Goldman-Rakic PS, 1998. Noise stress impairs prefrontal cortical cognitive function in monkeys: evidence for a hyperdopaminergic mechanism. Arch. Gen. Psychiatry 55, 362–368. - PubMed

Substances