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

Brain Research
Mary Gannon, Qin Wang

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.

Citations

Aug 14, 2018·Frontiers in Molecular Neuroscience·Giampiero LeanzaRobert Zorec
Jan 17, 2020·Science Translational Medicine·Fang ZhangQin Wang
May 10, 2020·International Journal of Molecular Sciences·Md Tanvir KabirMohamed M Abdel-Daim
Nov 16, 2020·The European Journal of Neuroscience·Tony JamesNathan A Smith
Dec 29, 2020·Frontiers in Aging Neuroscience·Robert A Culibrk, Mariah S Hahn
Feb 3, 2021·International Journal of Molecular Sciences·Rola A Bekdash
May 31, 2021·Clinical Neurology and Neurosurgery·Paul J Fitzgerald
Jun 9, 2021·Seminars in Cell & Developmental Biology·Mara Mather
Jul 25, 2021·International Journal of Molecular Sciences·Paul J Fitzgerald
Jul 15, 2021·Journal of Neuroscience Research·Christopher G Hart, Soheila Karimi-Abdolrezaee

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