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Immunosenescence and Aging: Neuroinflammation Is a Prominent Feature of Alzheimer’s Disease and Is a Likely Contributor to Neurodegenerative Disease Pathogenesis

Alzheimer’s disease (AD) is a chronic multifactorial and complex neuro-degenerative disorder characterized by memory impairment and the loss of cognitive ability, which is a problem affecting the elderly. The pathological intracellular accumulation of abnormally phosphorylated Tau proteins, forming...

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Autor principal: Bowirrat, Abdalla
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9698256/
https://www.ncbi.nlm.nih.gov/pubmed/36579548
http://dx.doi.org/10.3390/jpm12111817
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author Bowirrat, Abdalla
author_facet Bowirrat, Abdalla
author_sort Bowirrat, Abdalla
collection PubMed
description Alzheimer’s disease (AD) is a chronic multifactorial and complex neuro-degenerative disorder characterized by memory impairment and the loss of cognitive ability, which is a problem affecting the elderly. The pathological intracellular accumulation of abnormally phosphorylated Tau proteins, forming neurofibrillary tangles, and extracellular amyloid-beta (Aβ) deposition, forming senile plaques, as well as neural disconnection, neural death and synaptic dysfunction in the brain, are hallmark pathologies that characterize AD. The prevalence of the disease continues to increase globally due to the increase in longevity, quality of life, and medical treatment for chronic diseases that decreases the mortality and enhance the survival of elderly. Medical awareness and the accurate diagnosis of the disease also contribute to the high prevalence observed globally. Unfortunately, no definitive treatment exists that can be used to modify the course of AD, and no available treatment is capable of mitigating the cognitive decline or reversing the pathology of the disease as of yet. A plethora of hypotheses, ranging from the cholinergic theory and dominant Aβ cascade hypothesis to the abnormally excessive phosphorylated Tau protein hypothesis, have been reported. Various explanations for the pathogenesis of AD, such as the abnormal excitation of the glutamate system and mitochondrial dysfunction, have also been suggested. Despite the continuous efforts to deliver significant benefits and an effective treatment for this distressing, globally attested aging illness, multipronged approaches and strategies for ameliorating the disease course based on knowledge of the underpinnings of the pathogenesis of AD are urgently needed. Immunosenescence is an immune deficit process that appears with age (inflammaging process) and encompasses the remodeling of the lymphoid organs, leading to alterations in the immune function and neuroinflammation during advanced aging, which is closely linked to the outgrowth of infections, autoimmune diseases, and malignant cancers. It is well known that long-standing inflammation negatively influences the brain over the course of a lifetime due to the senescence of the immune system. Herein, we aim to trace the role of the immune system in the pathogenesis of AD. Thus, we explore alternative avenues, such as neuroimmune involvement in the pathogenesis of AD. We determine the initial triggers of neuroinflammation, which is an early episode in the pre-symptomatic stages of AD and contributes to the advancement of the disease, and the underlying key mechanisms of brain damage that might aid in the development of therapeutic strategies that can be used to combat this devastating disease. In addition, we aim to outline the ways in which different aspects of the immune system, both in the brain and peripherally, behave and thus to contribute to AD.
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spelling pubmed-96982562022-11-26 Immunosenescence and Aging: Neuroinflammation Is a Prominent Feature of Alzheimer’s Disease and Is a Likely Contributor to Neurodegenerative Disease Pathogenesis Bowirrat, Abdalla J Pers Med Review Alzheimer’s disease (AD) is a chronic multifactorial and complex neuro-degenerative disorder characterized by memory impairment and the loss of cognitive ability, which is a problem affecting the elderly. The pathological intracellular accumulation of abnormally phosphorylated Tau proteins, forming neurofibrillary tangles, and extracellular amyloid-beta (Aβ) deposition, forming senile plaques, as well as neural disconnection, neural death and synaptic dysfunction in the brain, are hallmark pathologies that characterize AD. The prevalence of the disease continues to increase globally due to the increase in longevity, quality of life, and medical treatment for chronic diseases that decreases the mortality and enhance the survival of elderly. Medical awareness and the accurate diagnosis of the disease also contribute to the high prevalence observed globally. Unfortunately, no definitive treatment exists that can be used to modify the course of AD, and no available treatment is capable of mitigating the cognitive decline or reversing the pathology of the disease as of yet. A plethora of hypotheses, ranging from the cholinergic theory and dominant Aβ cascade hypothesis to the abnormally excessive phosphorylated Tau protein hypothesis, have been reported. Various explanations for the pathogenesis of AD, such as the abnormal excitation of the glutamate system and mitochondrial dysfunction, have also been suggested. Despite the continuous efforts to deliver significant benefits and an effective treatment for this distressing, globally attested aging illness, multipronged approaches and strategies for ameliorating the disease course based on knowledge of the underpinnings of the pathogenesis of AD are urgently needed. Immunosenescence is an immune deficit process that appears with age (inflammaging process) and encompasses the remodeling of the lymphoid organs, leading to alterations in the immune function and neuroinflammation during advanced aging, which is closely linked to the outgrowth of infections, autoimmune diseases, and malignant cancers. It is well known that long-standing inflammation negatively influences the brain over the course of a lifetime due to the senescence of the immune system. Herein, we aim to trace the role of the immune system in the pathogenesis of AD. Thus, we explore alternative avenues, such as neuroimmune involvement in the pathogenesis of AD. We determine the initial triggers of neuroinflammation, which is an early episode in the pre-symptomatic stages of AD and contributes to the advancement of the disease, and the underlying key mechanisms of brain damage that might aid in the development of therapeutic strategies that can be used to combat this devastating disease. In addition, we aim to outline the ways in which different aspects of the immune system, both in the brain and peripherally, behave and thus to contribute to AD. MDPI 2022-11-02 /pmc/articles/PMC9698256/ /pubmed/36579548 http://dx.doi.org/10.3390/jpm12111817 Text en © 2022 by the author. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Bowirrat, Abdalla
Immunosenescence and Aging: Neuroinflammation Is a Prominent Feature of Alzheimer’s Disease and Is a Likely Contributor to Neurodegenerative Disease Pathogenesis
title Immunosenescence and Aging: Neuroinflammation Is a Prominent Feature of Alzheimer’s Disease and Is a Likely Contributor to Neurodegenerative Disease Pathogenesis
title_full Immunosenescence and Aging: Neuroinflammation Is a Prominent Feature of Alzheimer’s Disease and Is a Likely Contributor to Neurodegenerative Disease Pathogenesis
title_fullStr Immunosenescence and Aging: Neuroinflammation Is a Prominent Feature of Alzheimer’s Disease and Is a Likely Contributor to Neurodegenerative Disease Pathogenesis
title_full_unstemmed Immunosenescence and Aging: Neuroinflammation Is a Prominent Feature of Alzheimer’s Disease and Is a Likely Contributor to Neurodegenerative Disease Pathogenesis
title_short Immunosenescence and Aging: Neuroinflammation Is a Prominent Feature of Alzheimer’s Disease and Is a Likely Contributor to Neurodegenerative Disease Pathogenesis
title_sort immunosenescence and aging: neuroinflammation is a prominent feature of alzheimer’s disease and is a likely contributor to neurodegenerative disease pathogenesis
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9698256/
https://www.ncbi.nlm.nih.gov/pubmed/36579548
http://dx.doi.org/10.3390/jpm12111817
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