The Locus Coeruleus – Noradrenaline system: Looking into Alzheimer’s therapeutics with rose coloured glasses

• Published in: Biomedicine & pharmacotherapy 2022-07, Vol.151, p.113179-113179, Article 113179
• Main Authors: Behl, Tapan, Kaur, Ishnoor, Sehgal, Aayush, Singh, Sukhbir, Makeen, Hafiz A., Albratty, Mohammed, Alhazmi, Hassan A., Bhatia, Saurabh, Bungau, Simona
• Format: Article
• Language: English
• Subjects: Adrenergic system; Alzheimer Disease - metabolism; Alzheimer’s disease; Amyloid beta-Peptides - metabolism; Humans; Locus coeruleus; Locus Coeruleus - physiology; Neurotransmitters; Noradrenaline; Norepinephrine - metabolism; Plaque, Amyloid - pathology; tau Proteins - metabolism
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2022.113179

Owing to the challenging ethos of global healthcare system, the Alzheimer’s Disease (AD) researchers are consistently striving for a suitable target for disease amelioration. Besides the neurotransmitter release by neurons, the cells release tau proteins and amyloid peptides, within the extracellular vacancies, aggregating into tangles and plaques (AD pathological hallmarks). During neuro-stimulation, release of neuromodulator noradrenaline (NA), contained in the locus coeruleus (LC), exerts a significant impact on the neurons and microglia. The production of amyloid-β (Aβ) and hyperphosphorylation of tau proteins are affected by the α2A and β adrenoreceptors, parallel to influencing their clearance. The manuscript entails a detailed understanding of the LC-NA system, as a possible avenue in AD management. The authors provide a comprehensive data on AD pathology and its link with LC neuroanatomical projections, followed by the pathogenic implications of LC-NA system in AD. The data also integrates numerous studies from online databases, evidently supporting the loss of the system integrity in AD patients, and the impact of the sympathetic system on specific AD hallmarks. Thus, the objective of this review is to compile a wide compendium of studies, for the convenience of the neuro-researchers, aiding in the establishment of a suitable therapeutic regimen for AD treatment. [Display omitted] •The AD pathological pathways and their correlation with LC.•Flaws in neuroanatomical projections in LC contributing to tau accumulation and AD.•Overview of the LC-NA system, loss of its integrity and pathogenic implications in AD.•Impact of adrenergic system on individual AD pathological hallmarks.