scholarly journals The link between chronic pain and Alzheimer’s disease

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Song Cao ◽  
Daniel W. Fisher ◽  
Tain Yu ◽  
Hongxin Dong
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Chronic Pain ◽  
Animal Studies ◽  
Microglial Activation ◽  
The Elderly ◽  
Therapeutic Interventions ◽  
Affective Component ◽  
Inflammatory Activation ◽  
Improve Patient

Abstract Chronic pain often occurs in the elderly, particularly in the patients with neurodegenerative disorders such as Alzheimer’s disease (AD). Although studies indicate that chronic pain correlates with cognitive decline, it is unclear whether chronic pain accelerates AD pathogenesis. In this review, we provide evidence that supports a link between chronic pain and AD and discuss potential mechanisms underlying this connection based on currently available literature from human and animal studies. Specifically, we describe two intertwined processes, locus coeruleus noradrenergic system dysfunction and neuroinflammation resulting from microglial pro-inflammatory activation in brain areas mediating the affective component of pain and cognition that have been found to influence both chronic pain and AD. These represent a pathological overlap that likely leads chronic pain to accelerate AD pathogenesis. Further, we discuss potential therapeutic interventions targeting noradrenergic dysfunction and microglial activation that may improve patient outcomes for those with chronic pain and AD.

scholarly journals Treatment with Bifidobacteria can suppress Aβ accumulation and neuroinflammation in APP/PS1 mice

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10262
Author(s):  
Qiong Wu ◽  
Qifa Li ◽  
Xuan Zhang ◽  
Michael Ntim ◽  
Xuefei Wu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Microglial Activation ◽  
Amyloid Β ◽  
The Elderly ◽  
Inflammatory Factors ◽  
Complex Disorder ◽  
Tnf Α ◽  
The Brain ◽  
Excessive Accumulation

Background Alzheimer’s disease (AD), being a complex disorder, is affected either by genetic or environmental factors or both. It is observed that there is an excessive accumulation of amyloid β (Aβ) in the extracellular space of the brain. AD is the first neurodegenerative disease in the elderly, and so far there is no effective treatment. In recent years, many studies have reported that Alzheimer’s disease has a relationship with gut microflora, indicating that regulating gut microbiota could offer therapeutic intervention for AD. This study explored the effect Bifidobacteria has in averting AD. Methods WT and APP/PS1 mice were used for the experiments. The mice were randomly assigned to four groups: WT group, WT + Bi group, AD group (APP/PS1 mouse) and AD + Bi group (Bifidobacteria-treated APP/PS1 mouse). Treatment with Bifidobacteria lasted for 6 months and mice were prepared for immunohistochemistry, immunofluorescence, Thioflavin S staining, Western blotting, PCR and Elisa quantitative assay. Results The results show that after 6 months of treatment with Bifidobacteria signiis to be lesficantly reduces Aβ deposition in cortex and hippocampus of AD mice. The level of insoluble Aβ in the hippocampus and cortex of AD+Bi mice was decreased compared with AD mice. Meanwhile, a significant decrease in the level of soluble Aβ in the cortex of AD+Bi mice but not in the hippocampus was observed. The activation of microglia and the release of inflammatory factors were also determined in this study. From the results, Bifidobacteria inhibited microglial activation and reduced IL-1β, TNF-α, IL-4, IL-6 and INF-γ release. Altogether, these results implied that Bifidobacteria can alleviate the pathological changes of AD through various effects.

scholarly journals Microglia in Alzheimer’s Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Ying Li ◽  
Meng-Shan Tan ◽  
Teng Jiang ◽  
Lan Tan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Microglial Activation ◽  
The Elderly ◽  
Inflammatory Factors ◽  
Dual Roles ◽  
Neuroprotective Effects ◽  
Regulatory Systems ◽  
Future Strategy ◽  
Review Current

Alzheimer’s disease (AD) is a familiar neurodegenerative disease in the elderly. In this paper, we will review current viewpoints of microglial activation, inflammatory regulatory systems, and their relationship with AD pathology and etiology. Microglia cells are macrophage and representative of the innate immune system in brain. AD brain is marked by obvious inflammatory features, in which microglial activation is the driving force.β-amyloid protein sedimentation activates microglia cells, which causes the inflammation in AD. Microglia cells have dual roles: they provoke the release of inflammatory factors and cytotoxins leading to neuronal injuries and death; on the other hand, they have the neuroprotective effects. Through this, we hope to illustrate that the anti-inflammatory defenses of neurons can be practiced in the future strategy for recuperating the balance between the levels of inflammatory mediators and immune regulators in AD.

scholarly journals Alzheimer's Disease: Another Target for Heparin Therapy

2009 ◽  
Vol 9 ◽  
pp. 891-908 ◽  
Author(s):  
Luigi Bergamaschini ◽  
Emanuela Rossi ◽  
Carlo Vergani ◽  
Maria Grazia De Simoni
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
The Elderly ◽  
Heparin Therapy ◽  
Therapeutic Interventions ◽  
Neuronal Viability ◽  
Β Protein ◽  
Tissue Changes

Alzheimer's disease (AD) is the leading cause of dementia and cognitive decline in the elderly. Brain tissue changes indicate that the two main proteins involved in AD are amyloid-β(A-β), which is associated with the formation of senile amyloid plaques, and tau, which is associated with the formation of neurofibrillary tangles. Although a central role for A-β in the pathogenesis of AD is indisputable, considerable evidence indicates that A-β production is not the sole culprit in AD pathology. AD is also accompanied by an inflammatory response that contributes to irreversible changes in neuronal viability and brain function, and accumulating evidence supports the pivotal role of complement and contact systems in its pathogenesis and progression. The complexity of AD pathology provides numerous potential targets for therapeutic interventions. Compounds that interact directly with A-β protein or interfere with its production and/or aggregation can reduce the inflammatory and neurotoxic effects of A-β, and heparin, a glycosaminoglycan mixture currently used in the prophylaxis and treatment of thrombosis, might be a candidate, as recent research has been extended to consider its nonanticoagulant properties, including its modulation of various proteases and anti-inflammatory activity.

scholarly journals Sirtuins as Potential Therapeutic Targets for Mitigating Neuroinflammation Associated With Alzheimer’s Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Kurukulasooriya Kavindya Madushani Fernando ◽  
Yasanandana Supunsiri Wijayasinghe
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Microglial Activation ◽  
Neurodegenerative Disorder ◽  
Therapeutic Interventions ◽  
Cellular Processes ◽  
Dependent Protein ◽  
The Central Nervous System ◽  
Β Amyloid ◽  
With Memory

Alzheimer’s disease (AD) is the most common neurodegenerative disorder, which is associated with memory deficit and global cognitive decline. Age is the greatest risk factor for AD and, in recent years, it is becoming increasingly appreciated that aging-related neuroinflammation plays a key role in the pathogenesis of AD. The presence of β-amyloid plaques and neurofibrillary tangles are the primary pathological hallmarks of AD; defects which can then activate a cascade of molecular inflammatory pathways in glial cells. Microglia, the resident macrophages in the central nervous system (CNS), are the major triggers of inflammation; a response which is typically intended to prevent further damage to the CNS. However, persistent microglial activation (i.e., neuroinflammation) is toxic to both neurons and glia, which then leads to neurodegeneration. Growing evidence supports a central role for sirtuins in the regulation of neuroinflammation. Sirtuins are NAD+-dependent protein deacetylases that modulate a number of cellular processes associated with inflammation. This review examines the latest findings regarding AD-associated neuroinflammation, mainly focusing on the connections among the microglial molecular pathways of inflammation. Furthermore, we highlight the biology of sirtuins, and their role in neuroinflammation. Suppression of microglial activity through modulation of the sirtuin activity has now become a key area of research, where progress in therapeutic interventions may slow the progression of Alzheimer’s disease.

Effect Of Nhexane Extract Of Caryota No Seed On Markers Of Neurodegeneration And Fecundity In Drosophila Melanogaster

2020 ◽  
Vol 6 (5) ◽  
pp. 1-7
Author(s):  
Chinonye A Maduagwuna ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drosophila Melanogaster ◽  
Neurodegenerative Diseases ◽  
Cognitive Functions ◽  
The Elderly ◽  
Common Cause ◽  
Chronic Neuroinflammation

Study background: Chronic neuroinflammation is a common emerging hallmark of several neurodegenerative diseases. Alzheimer’s Disease (AD) is the most common cause of dementia among the elderly and is characterized by loss of memory and other cognitive functions.

Therapeutic Interventions for the Suppression of Alzheimer’s Disease: Quest for a Remedy

2015 ◽  
Vol 16 (5) ◽  
pp. 346-353 ◽  
Author(s):  
Naveed Fazili ◽  
Aabgeena Naeem ◽  
Ghulam Ashraf ◽  
Siew Gan ◽  
Mohammad Kamal
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Interventions

Molecular Genetics of Early- and Late-Onset Alzheimer’s Disease

2020 ◽  
Vol 20 ◽  
Author(s):  
Md. Sahab Uddin ◽  
Sharifa Hasana ◽  
Md. Farhad Hossain ◽  
Md. Siddiqul Islam ◽  
Tapan Behl ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Massively Parallel Sequencing ◽  
Late Onset ◽  
Current Knowledge ◽  
The Elderly ◽  
Apoe Ε4 ◽  
Sequencing Technologies ◽  
Genetic Components ◽  
Ε4 Allele

: Alzheimer’s disease (AD) is the most common form of dementia in the elderly and this complex disorder is associated with environmental as well as genetic components. Early-onset AD (EOAD) and late-onset AD (LOAD, more common) are major identified types of AD. The genetics of EOAD is extensively understood with three genes variants such as APP, PSEN1, and PSEN2 leading to disease. On the other hand, some common alleles including APOE are effectively associated with LOAD identified but the genetics of LOAD is not clear to date. It has been accounted that about 5% to 10% of EOAD patients can be explained through mutations in the three familiar genes of EOAD. The APOE ε4 allele augmented the severity of EOAD risk in carriers, and APOE ε4 allele was considered as a hallmark of EOAD. A great number of EOAD patients, who are not genetically explained, indicate that it is not possible to identify disease- triggering genes yet. Although several genes have been identified through using the technology of next-generation sequencing in EOAD families including SORL1, TYROBP, and NOTCH3. A number of TYROBP variants were identified through exome sequencing in EOAD patients and these TYROBP variants may increase the pathogenesis of EOAD. The existence of ε4 allele is responsible for increasing the severity of EOAD. However, several ε4 allele carriers live into their 90s that propose the presence of other LOAD genetic as well as environmental risk factors that are not identified yet. It is urgent to find out missing genetics of EOAD and LOAD etiology to discover new potential genetics facets which will assist to understand the pathological mechanism of AD. These investigations should contribute to developing a new therapeutic candidate for alleviating, reversing and preventing AD. This article based on current knowledge represents the overview of the susceptible genes of EOAD, and LOAD. Next, we represent the probable molecular mechanism which might elucidate the genetic etiology of AD and highlight the role of massively parallel sequencing technologies for novel gene discoveries.

Easy Screening for Mild Alzheimer's Disease and Mild Cognitive Impairment from Elderly Speech

2018 ◽  
Vol 15 (2) ◽  
pp. 104-110 ◽  
Author(s):  
Shohei Kato ◽  
Akira Homma ◽  
Takuto Sakuma
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Characteristic Curve ◽  
Linear Regression Analysis ◽  
Speech Sound ◽  
The Elderly ◽  
Speech Sounds ◽  
Mel Frequency Cepstral Coefficients

Objective: This study presents a novel approach for early detection of cognitive impairment in the elderly. The approach incorporates the use of speech sound analysis, multivariate statistics, and data-mining techniques. We have developed a speech prosody-based cognitive impairment rating (SPCIR) that can distinguish between cognitively normal controls and elderly people with mild Alzheimer's disease (mAD) or mild cognitive impairment (MCI) using prosodic signals extracted from elderly speech while administering a questionnaire. Two hundred and seventy-three Japanese subjects (73 males and 200 females between the ages of 65 and 96) participated in this study. The authors collected speech sounds from segments of dialogue during a revised Hasegawa's dementia scale (HDS-R) examination and talking about topics related to hometown, childhood, and school. The segments correspond to speech sounds from answers to questions regarding birthdate (T1), the name of the subject's elementary school (T2), time orientation (Q2), and repetition of three-digit numbers backward (Q6). As many prosodic features as possible were extracted from each of the speech sounds, including fundamental frequency, formant, and intensity features and mel-frequency cepstral coefficients. They were refined using principal component analysis and/or feature selection. The authors calculated an SPCIR using multiple linear regression analysis. Conclusion: In addition, this study proposes a binary discrimination model of SPCIR using multivariate logistic regression and model selection with receiver operating characteristic curve analysis and reports on the sensitivity and specificity of SPCIR for diagnosis (control vs. MCI/mAD). The study also reports discriminative performances well, thereby suggesting that the proposed approach might be an effective tool for screening the elderly for mAD and MCI.

scholarly journals Tau and TDP-43 synergy: a novel therapeutic target for sporadic late-onset Alzheimer’s disease

GeroScience ◽  
2021 ◽  
Author(s):  
Caitlin S. Latimer ◽  
Nicole F. Liachko
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Late Onset ◽  
Hippocampal Sclerosis ◽  
Model Organism ◽  
Amyloid Β ◽  
Underlying Disease ◽  
Therapeutic Interventions ◽  
Disease Biology ◽  
Rapid Cognitive Decline

AbstractAlzheimer’s disease (AD) is traditionally defined by the presence of two types of protein aggregates in the brain: amyloid plaques comprised of the protein amyloid-β (Aβ) and neurofibrillary tangles containing the protein tau. However, a large proportion (up to 57%) of AD patients also have TDP-43 aggregates present as an additional comorbid pathology. The presence of TDP-43 aggregates in AD correlates with hippocampal sclerosis, worse brain atrophy, more severe cognitive impairment, and more rapid cognitive decline. In patients with mixed Aβ, tau, and TDP-43 pathology, TDP-43 may interact with neurodegenerative processes in AD, worsening outcomes. While considerable progress has been made to characterize TDP-43 pathology in AD and late-onset dementia, there remains a critical need for mechanistic studies to understand underlying disease biology and develop therapeutic interventions. This perspectives article reviews the current understanding of these processes from autopsy cohort studies and model organism-based research, and proposes targeting neurotoxic synergies between tau and TDP-43 as a new therapeutic strategy for AD with comorbid TDP-43 pathology.

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