The Contribution of the Locus Coeruleus-Noradrenaline System Degeneration During the Progression of Alzheimer's Disease

Overview

Journal Biology (Basel)

Publisher MDPI

Specialty Biology

Date 2022 Dec 23

PMID 36552331

Authors

Dilek Mercan

Michael Thomas Heneka

Affiliations

Soon will be listed here.

Abstract

Alzheimer's disease (AD), which is characterized by extracellular accumulation of amyloid-beta peptide and intracellular aggregation of hyperphosphorylated tau, is the most common form of dementia. Memory loss, cognitive decline and disorientation are the ultimate consequences of neuronal death, synapse loss and neuroinflammation in AD. In general, there are many brain regions affected but neuronal loss in the locus coeruleus (LC) is one of the earliest indicators of neurodegeneration in AD. Since the LC is the main source of noradrenaline (NA) in the brain, degeneration of the LC in AD leads to decreased NA levels, causing increased neuroinflammation, enhanced amyloid and tau burden, decreased phagocytosis and impairment in cognition and long-term synaptic plasticity. In this review, we summarized current findings on the locus coeruleus-noradrenaline system and consequences of its dysfunction which is now recognized as an important contributor to AD progression.

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References

Prieto G, Tong L, Smith E, Cotman C . TNFα and IL-1β but not IL-18 Suppresses Hippocampal Long-Term Potentiation Directly at the Synapse. Neurochem Res. 2018; 44(1):49-60. PMC: 6170724. DOI: 10.1007/s11064-018-2517-8. View

Ginhoux F, Guilliams M . Tissue-Resident Macrophage Ontogeny and Homeostasis. Immunity. 2016; 44(3):439-449. DOI: 10.1016/j.immuni.2016.02.024. View

Sun L, Perakyla J, Holm K, Haapasalo J, Lehtimaki K, Ogawa K . Vagus nerve stimulation improves working memory performance. J Clin Exp Neuropsychol. 2017; 39(10):954-964. DOI: 10.1080/13803395.2017.1285869. View

Pugh P, Vidgeon-Hart M, Ashmeade T, Culbert A, Seymour Z, Perren M . Repeated administration of the noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) modulates neuroinflammation and amyloid plaque load in mice bearing amyloid precursor protein and presenilin-1 mutant transgenes. J Neuroinflammation. 2007; 4:8. PMC: 1810243. DOI: 10.1186/1742-2094-4-8. View

Braak H, Del Tredici K . Alzheimer's pathogenesis: is there neuron-to-neuron propagation?. Acta Neuropathol. 2011; 121(5):589-95. DOI: 10.1007/s00401-011-0825-z. View

Dello Russo C, Boullerne A, Gavrilyuk V, Feinstein D . Inhibition of microglial inflammatory responses by norepinephrine: effects on nitric oxide and interleukin-1beta production. J Neuroinflammation. 2004; 1(1):9. PMC: 500870. DOI: 10.1186/1742-2094-1-9. View

Serpente M, Bonsi R, Scarpini E, Galimberti D . Innate immune system and inflammation in Alzheimer's disease: from pathogenesis to treatment. Neuroimmunomodulation. 2014; 21(2-3):79-87. DOI: 10.1159/000356529. View

McGaugh J . The amygdala modulates the consolidation of memories of emotionally arousing experiences. Annu Rev Neurosci. 2004; 27:1-28. DOI: 10.1146/annurev.neuro.27.070203.144157. View

Evans A, Ardestani P, Yi B, Park H, Lam R, Shamloo M . Beta-adrenergic receptor antagonism is proinflammatory and exacerbates neuroinflammation in a mouse model of Alzheimer's Disease. Neurobiol Dis. 2020; 146:105089. PMC: 7686098. DOI: 10.1016/j.nbd.2020.105089. View

10.

Sano M, Ernesto C, Thomas R, Klauber M, Schafer K, Grundman M . A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study. N Engl J Med. 1997; 336(17):1216-22. DOI: 10.1056/NEJM199704243361704. View

11.

Hoover B, Reed M, Su J, Penrod R, Kotilinek L, Grant M . Tau mislocalization to dendritic spines mediates synaptic dysfunction independently of neurodegeneration. Neuron. 2010; 68(6):1067-81. PMC: 3026458. DOI: 10.1016/j.neuron.2010.11.030. View

12.

Bonisch H, Bruss M . The noradrenaline transporter of the neuronal plasma membrane. Ann N Y Acad Sci. 1994; 733:193-202. DOI: 10.1111/j.1749-6632.1994.tb17269.x. View

13.

Ramos B, Arnsten A . Adrenergic pharmacology and cognition: focus on the prefrontal cortex. Pharmacol Ther. 2007; 113(3):523-36. PMC: 2151919. DOI: 10.1016/j.pharmthera.2006.11.006. View

14.

Wong D, Threlkeld P, Best K, Bymaster F . A new inhibitor of norepinephrine uptake devoid of affinity for receptors in rat brain. J Pharmacol Exp Ther. 1982; 222(1):61-5. View

15.

Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole G . Inflammation and Alzheimer's disease. Neurobiol Aging. 2000; 21(3):383-421. PMC: 3887148. DOI: 10.1016/s0197-4580(00)00124-x. View

16.

Hoeffel G, Ginhoux F . Ontogeny of Tissue-Resident Macrophages. Front Immunol. 2015; 6:486. PMC: 4585135. DOI: 10.3389/fimmu.2015.00486. View

17.

Rosas-Ballina M, Olofsson P, Ochani M, Valdes-Ferrer S, Levine Y, Reardon C . Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit. Science. 2011; 334(6052):98-101. PMC: 4548937. DOI: 10.1126/science.1209985. View

18.

Aston-Jones G, Bloom F . Activity of norepinephrine-containing locus coeruleus neurons in behaving rats anticipates fluctuations in the sleep-waking cycle. J Neurosci. 1981; 1(8):876-86. PMC: 6564235. View

19.

Evans L, Wassmer T, Fraser G, Smith J, Perkinton M, Billinton A . Extracellular Monomeric and Aggregated Tau Efficiently Enter Human Neurons through Overlapping but Distinct Pathways. Cell Rep. 2018; 22(13):3612-3624. PMC: 5896171. DOI: 10.1016/j.celrep.2018.03.021. View

20.

Adolfsson R, Gottfries C, ROOS B, Winblad B . Changes in the brain catecholamines in patients with dementia of Alzheimer type. Br J Psychiatry. 1979; 135:216-23. DOI: 10.1192/bjp.135.3.216. View