Abstract
Alzheimer’s disease (AD) represents the most prevalent form of dementia in the elderly. However, the pathological mechanisms underlying the development and progression of AD are only partially understood. To date, the accumulated clinical and experimental evidence indicate that the locus coeruleus (LC), the main source of brain’s norepinephrine, represents “the epicenter” of pathology leading to the development of AD. Evidence for this includes observations that neurons of the LC modulate several processes that are altered in brains of AD patients, including synaptic plasticity, neuroinflammation, neuronal metabolism, and blood-brain-barrier permeability. Moreover, the LC undergoes significant degeneration in the brains of AD patients and is considered a source of the prion-like spreading of tau pathology to forebrain structures innervated by the noradrenergic neurons of the LC. Furthermore, lesions of the LC exaggerate AD-related pathology, while augmentation of the brain’s noradrenergic neurotransmission reduces both neuroinflammation and cognitive decline. We hypothesize that better understanding the role of the LC neurons in AD pathogenesis may lead to development of new strategies for the treatment of AD.
Keywords: Alzheimer's disease, blood-brain-barrier, locus coeruleus, neuroinflammation, plasticity, tau protein.
Current Alzheimer Research
Title:Locus (Coeruleus) Minoris Resistentiae in Pathogenesis of Alzheimer’s Disease
Volume: 11 Issue: 10
Author(s): Boris Mravec, Katarina Lejavova and Veronika Cubinkova
Affiliation:
Keywords: Alzheimer's disease, blood-brain-barrier, locus coeruleus, neuroinflammation, plasticity, tau protein.
Abstract: Alzheimer’s disease (AD) represents the most prevalent form of dementia in the elderly. However, the pathological mechanisms underlying the development and progression of AD are only partially understood. To date, the accumulated clinical and experimental evidence indicate that the locus coeruleus (LC), the main source of brain’s norepinephrine, represents “the epicenter” of pathology leading to the development of AD. Evidence for this includes observations that neurons of the LC modulate several processes that are altered in brains of AD patients, including synaptic plasticity, neuroinflammation, neuronal metabolism, and blood-brain-barrier permeability. Moreover, the LC undergoes significant degeneration in the brains of AD patients and is considered a source of the prion-like spreading of tau pathology to forebrain structures innervated by the noradrenergic neurons of the LC. Furthermore, lesions of the LC exaggerate AD-related pathology, while augmentation of the brain’s noradrenergic neurotransmission reduces both neuroinflammation and cognitive decline. We hypothesize that better understanding the role of the LC neurons in AD pathogenesis may lead to development of new strategies for the treatment of AD.
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Mravec Boris, Lejavova Katarina and Cubinkova Veronika, Locus (Coeruleus) Minoris Resistentiae in Pathogenesis of Alzheimer’s Disease, Current Alzheimer Research 2014; 11 (10) . https://dx.doi.org/10.2174/1567205011666141107130505
DOI https://dx.doi.org/10.2174/1567205011666141107130505 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
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Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...read more
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