The involvement of the Locus Coeruleus (LC)–noradrenaline (NA) system in sleep regulation and its association with Alzheimer’s disease.

Grishin, Svyatoslav (2023) The involvement of the Locus Coeruleus (LC)–noradrenaline (NA) system in sleep regulation and its association with Alzheimer’s disease. Bachelor's Thesis, Life Science and Technology.

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Abstract

Reported Locus Coeruleus (LC) cell death in Alzheimer’s disease (AD) is extensive. However, the connection between LC-NA and AD was largely overlooked in the research. The LC, being the first structure in the brain to express AD associated neuropathology, is sensitive to neurodegenerative processes, suggesting a significant role in early AD development. Disturbances in the LC-NA system, along with sleep impairment, can trigger a cascade of neuroinflammatory processes, leading to chronic low-grade inflammation, blood brain barrier (BBB) disruption, and eventual AD pathogenesis. This is further worsened by the impairment in the glymphatic system - a key pathway for the removal of neurotoxic waste like β-amyloid during sleep - due to sleep-wake dysregulation. Generally, sleep disturbances are often exacerbated by LC-NA dysregulation, and are associated with elevated Aβ or tau levels, thereby intensifying AD pathogenesis. This review discusses potential therapeutic interventions targeting the LC-NA system, including the enhancement of REM/NREM sleep and drugs like AChE inhibitors and orexin antagonists. Notably, the use of PDE4 inhibitors presents a promising strategy to address both AD and sleep pathologies. Ultimately, investigating the intricate interplay between the LC-NA system, sleep disruption, and neuroinflammatory processes is imperative to deepen the understanding of AD.

Item Type:	Thesis (Bachelor's Thesis)
Supervisor name:	Eisel, U.L.M. and Havekes, R.
Degree programme:	Life Science and Technology
Thesis type:	Bachelor's Thesis
Language:	English
Date Deposited:	04 Oct 2023 10:24
Last Modified:	04 Oct 2023 10:24
URI:	https://fse.studenttheses.ub.rug.nl/id/eprint/31495

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