Neuroinflammatory Signaling in the Pathogenesis of Alzheimer’s Disease

2021 ◽  
Vol 19 ◽  
Author(s):  
Md. Sahab Uddin ◽  
Md. Tanvir Kabir ◽  
Maroua Jalouli ◽  
Md. Ataur Rahman ◽  
Philippe Jeandet ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Innate Immune ◽  
Misfolded Proteins ◽  
Inflammatory Signaling ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
Immunological Mechanisms ◽  
The Brain

: Alzheimer’s disease (AD) is a chronic neurodegenerative disease characterized by the formation of intracellular neurofibrillary tangles (NFTs) and extracellular amyloid plaques. Growing evidence has suggested that AD pathogenesis is not only limited to the neuronal compartment but also strongly interacts with immunological processes in the brain. On the other hand, aggregated and misfolded proteins can bind with pattern recognition receptors located on astroglia and microglia and can in turn induce an innate immune response, characterized by the release of inflammatory mediators, ultimately playing a role in both the severity and the progression of the disease. It has been reported by genome-wide analysis that several genes which elevate the risk for sporadic AD encode for factors controlling the inflammatory response and glial clearance of misfolded proteins. Obesity and systemic inflammation are examples of external factors which may interfere with the immunological mechanisms of the brain and can induce disease progression. In this review, we discussed the mechanisms and essential role of inflammatory signaling pathways in AD pathogenesis. Indeed, interfering with immune processes and modulation of risk factors may lead to future therapeutic or preventive AD approaches.

scholarly journals Conditional genetic deletion of CSF1 receptor in microglia ameliorates the physiopathology of Alzheimer’s disease

2020 ◽  
Author(s):  
Vincent Pons ◽  
Pascal Lévesque ◽  
Marie-Michèle Plande ◽  
Serge Rivest
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Innate Immune ◽  
Compensatory Mechanism ◽  
Knock Out ◽  
Genetic Deletion ◽  
The Impact ◽  
The Brain

Abstract BackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia in the world. Microglia are the innate immune cells of CNS, their proliferation, activation and survival in pathologic and healthy brain have previously been shown to be highly dependent on CSF1R.MethodsHere we investigate the impact of such receptor on AD etiology and microglia. We deleted CSF1R using Cre/Lox system, the knock-out (KO) is restricted to microglia in the APP/PS1 mouse model. We induced the knock-out at 3-month-old, before plaque formation and evaluated both 6 and 8-month-old groups of mice.ResultsOur findings demonstrated that CSF1R KO did not impair microglial survival and proliferation at 6 and 8 months of age in APP cKO compared to their littermate controls groups APPSwe/PS1. We have also shown that cognitive decline is delayed in CSF1R-deleted mice. Ameliorations of AD etiology is associated with a decrease in plaque volume in cortex and hippocampus area. A compensating system seems to take place following the knock-out, since TREM2/β-Catenin and IL-34 expression are significantly increased. Such a compensatory mechanism may promote microglial survival and phagocytosis of Aβ in the brain.ConclusionsOur results provide new insights on the role of CSF1R in microglia and how it interacts with the TREM2/β-Catenin and IL-34 system to clear Aβ and ameliorates the physiopathology of AD.

scholarly journals Conditional Genetic Deletion of CSF1 Receptor in Microglia Ameliorates the Physiopathology of Alzheimer’s Disease

2020 ◽  
Author(s):  
Vincent Pons ◽  
Pascal Lévesque ◽  
Marie-Michèle Plande ◽  
Serge Rivest
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Innate Immune ◽  
Compensatory Mechanism ◽  
Knock Out ◽  
Genetic Deletion ◽  
The Impact ◽  
The Brain

Abstract Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia in the world. Microglia are the innate immune cells of CNS, their proliferation, activation and survival in pathologic and healthy brain have previously been shown to be highly dependent on CSF1R. Methods: Here we investigate the impact of such receptor on AD etiology and microglia. We deleted CSF1R using Cre/Lox system, the knock-out (KO) is restricted to microglia in the APP/PS1 mouse model. We induced the knock-out at 3-month-old, before plaque formation and evaluated both 6 and 8-month-old groups of mice. Results: Our findings demonstrated that CSF1R KO did not impair microglial survival and proliferation at 6 and 8 months of age in APP cKO compared to their littermate controls groups APPSwe/PS1. We have also shown that cognitive decline is delayed in CSF1R-deleted mice. Ameliorations of AD etiology is associated with a decrease in plaque volume in cortex and hippocampus area. A compensating system seems to take place following the knock-out, since TREM2/β-Catenin and IL-34 expression are significantly increased. Such a compensatory mechanism may promote microglial survival and phagocytosis of Aβ in the brain. Conclusions: Our results provide new insights on the role of CSF1R in microglia and how it interacts with the TREM2/β-Catenin and IL-34 system to clear Aβ and ameliorates the physiopathology of AD.

scholarly journals Conditional genetic deletion of CSF1 receptor in microglia ameliorates the physiopathology of Alzheimer’s disease

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Vincent Pons ◽  
Pascal Lévesque ◽  
Marie-Michèle Plante ◽  
Serge Rivest
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Innate Immune ◽  
Compensatory Mechanism ◽  
Littermate Control ◽  
Genetic Deletion ◽  
The Impact ◽  
The Brain

Abstract Background Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia in the world. Microglia are the innate immune cells of CNS; their proliferation, activation, and survival in pathologic and healthy brain have previously been shown to be highly dependent on CSF1R. Methods Here, we investigate the impact of such receptor on AD etiology and microglia. We deleted CSF1R using Cre/Lox system; the knockout (KO) is restricted to microglia in the APP/PS1 mouse model. We induced the knockout at 3 months old, before plaque formation, and evaluated both 6- and 8-month-old groups of mice. Results Our findings demonstrated that CSF1R KO did not impair microglial survival and proliferation at 6 and 8 months of age in APP cKO compared to their littermate-control groups APPSwe/PS1. We have also shown that cognitive decline is delayed in CSF1R-deleted mice. Ameliorations of AD etiology are associated with a decrease in plaque volume in the cortex and hippocampus area. A compensating system seems to take place following the knockout, since TREM2/β-Catenin and IL-34 expression are significantly increased. Such a compensatory mechanism may promote microglial survival and phagocytosis of Aβ in the brain. Conclusions Our results provide new insights on the role of CSF1R in microglia and how it interacts with the TREM2/β-Catenin and IL-34 system to clear Aβ and ameliorates the physiopathology of AD.

Role of Adaptive Immune and Impacts of Risk Factors on Adaptive Immune in Alzheimer’s Disease: Are Immunotherapies Effective or Off-Target?

2021 ◽  
pp. 107385842098722
Author(s):  
Mingchao Shi ◽  
Fengna Chu ◽  
Xiaoping Tian ◽  
Qiaolifan Aerqin ◽  
Feiqi Zhu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Innate Immune ◽  
Adaptive Immune ◽  
Immune Mediators ◽  
Pathogenic Factors ◽  
The Brain ◽  
Cellular Alterations

The pathogenesis of Alzheimer’s disease (AD) is complex. Still it remains unclear, which resulted in all efforts for AD treatments with targeting the pathogenic factors unsuccessful over past decades. It has been evidenced that the innate immune is strongly implicated in the pathogenesis of AD. However, the role of adaptive immune in AD remains mostly unknown and the results obtained were controversial. In the review, we summarized recent studies and showed that the molecular and cellular alterations in AD patients and its animal models involving T cells and B cells as well as immune mediators of adaptive immune occur not only in the peripheral blood but also in the brain and the cerebrospinal fluid. The risk factors that cause AD contribute to AD progress by affecting the adaptive immune, indicating that adaptive immunity proposes a pivotal role in this disease. It may provide a possible basis for applying immunotherapy in AD and further investigates whether the immunotherapies are effective or off-target?

Role of Nanomedicines in Delivery of Anti-Acetylcholinesterase Compounds to the Brain in Alzheimer’s Disease

2014 ◽  
Vol 13 (8) ◽  
pp. 1315-1324 ◽  
Author(s):  
Mohammad Ahmad ◽  
Javed Ahmad ◽  
Saima Amin ◽  
Mahfoozur Rahman ◽  
Mohammad Anwar ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
The Brain

scholarly journals Peptides Derived from Growth Factors to Treat Alzheimer’s Disease

2021 ◽  
Vol 22 (11) ◽  
pp. 6071
Author(s):  
Suzanne Gascon ◽  
Jessica Jann ◽  
Chloé Langlois-Blais ◽  
Mélanie Plourde ◽  
Christine Lavoie ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Growth Factors ◽  
Signaling Pathways ◽  
Brain Structures ◽  
Therapeutic Strategies ◽  
Native Proteins ◽  
Receptor Sites ◽  
The Brain

Alzheimer’s disease (AD) is a devastating neurodegenerative disease characterized by progressive neuron losses in memory-related brain structures. The classical features of AD are a dysregulation of the cholinergic system, the accumulation of amyloid plaques, and neurofibrillary tangles. Unfortunately, current treatments are unable to cure or even delay the progression of the disease. Therefore, new therapeutic strategies have emerged, such as the exogenous administration of neurotrophic factors (e.g., NGF and BDNF) that are deficient or dysregulated in AD. However, their low capacity to cross the blood–brain barrier and their exorbitant cost currently limit their use. To overcome these limitations, short peptides mimicking the binding receptor sites of these growth factors have been developed. Such peptides can target selective signaling pathways involved in neuron survival, differentiation, and/or maintenance. This review focuses on growth factors and their derived peptides as potential treatment for AD. It describes (1) the physiological functions of growth factors in the brain, their neuronal signaling pathways, and alteration in AD; (2) the strategies to develop peptides derived from growth factor and their capacity to mimic the role of native proteins; and (3) new advancements and potential in using these molecules as therapeutic treatments for AD, as well as their limitations.

scholarly journals Alzheimer’s Disease Pathogenesis: Role of Autophagy and Mitophagy Focusing in Microglia

2021 ◽  
Vol 22 (7) ◽  
pp. 3330
Author(s):  
Mehdi Eshraghi ◽  
Aida Adlimoghaddam ◽  
Amir Mahmoodzadeh ◽  
Farzaneh Sharifzad ◽  
Hamed Yasavoli-Sharahi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Target ◽  
Neurological Disorder ◽  
Inflammatory Cells ◽  
Disease Pathogenesis ◽  
Current Review ◽  
The Brain ◽  
Comprehensive Discussion

Alzheimer’s disease (AD) is a debilitating neurological disorder, and currently, there is no cure for it. Several pathologic alterations have been described in the brain of AD patients, but the ultimate causative mechanisms of AD are still elusive. The classic hallmarks of AD, including am-yloid plaques (Aβ) and tau tangles (tau), are the most studied features of AD. Unfortunately, all the efforts targeting these pathologies have failed to show the desired efficacy in AD patients so far. Neuroinflammation and impaired autophagy are two other main known pathologies in AD. It has been reported that these pathologies exist in AD brain long before the emergence of any clinical manifestation of AD. Microglia are the main inflammatory cells in the brain and are considered by many researchers as the next hope for finding a viable therapeutic target in AD. Interestingly, it appears that the autophagy and mitophagy are also changed in these cells in AD. Inside the cells, autophagy and inflammation interact in a bidirectional manner. In the current review, we briefly discussed an overview on autophagy and mitophagy in AD and then provided a comprehensive discussion on the role of these pathways in microglia and their involvement in AD pathogenesis.

scholarly journals The Role of Long Noncoding RNAs in Diabetic Alzheimer’s Disease

2018 ◽  
Vol 7 (11) ◽  
pp. 461 ◽  
Author(s):  
Young-Kook Kim ◽  
Juhyun Song
Keyword(s):  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Glucose Dysregulation ◽  
Near Future ◽  
The Brain

Long noncoding RNAs (lncRNAs) are involved in diverse physiological and pathological processes by modulating gene expression. They have been found to be dysregulated in the brain and cerebrospinal fluid of patients with neurodegenerative diseases, and are considered promising therapeutic targets for treatment. Among the various neurodegenerative diseases, diabetic Alzheimer’s disease (AD) has been recently emerging as an important issue due to several unexpected reports suggesting that metabolic issues in the brain, such as insulin resistance and glucose dysregulation, could be important risk factors for AD. To facilitate understanding of the role of lncRNAs in this field, here we review recent studies on lncRNAs in AD and diabetes, and summarize them with different categories associated with the pathogenesis of the diseases including neurogenesis, synaptic dysfunction, amyloid beta accumulation, neuroinflammation, insulin resistance, and glucose dysregulation. It is essential to understand the role of lncRNAs in the pathogenesis of diabetic AD from various perspectives for therapeutic utilization of lncRNAs in the near future.

scholarly journals Sex Differences and the Influence of Sex Hormones on Cognition through Adulthood and the Aging Process

2018 ◽  
Vol 8 (9) ◽  
pp. 163 ◽  
Author(s):  
Caroline Gurvich ◽  
Kate Hoy ◽  
Natalie Thomas ◽  
Jayashri Kulkarni
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sex Differences ◽  
Cognitive Functioning ◽  
Sex Hormones ◽  
Reproductive Function ◽  
Health And Disease ◽  
And Function ◽  
The Brain

Hormones of the hypothalamic-pituitary-gonadal (HPG) axis that regulate reproductive function have multiple effects on the development, maintenance and function of the brain. Sex differences in cognitive functioning have been reported in both health and disease, which may be partly attributed to sex hormones. The aim of the current paper was to provide a theoretical review of how sex hormones influence cognitive functioning across the lifespan as well as provide an overview of the literature on sex differences and the role of sex hormones in cognitive decline, specifically in relation to Alzheimer’s disease (AD). A summary of current hormone and sex-based interventions for enhancing cognitive functioning and/or reducing the risk of Alzheimer’s disease is also provided.

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