Pub Date : 2021-01-01Epub Date: 2021-09-10DOI: 10.23937/2643-4539/1710020
Troy T Rohn, James D Beck, Stephanie J Galla, Noail F Isho, Tanner B Pollock, Tarun Suresh, Arni Kulkarni, Tanya Sanghal, Eric J Hayden
The apolipoprotein E4 (APOE4) allele represents the single greatest risk factor for late-onset Alzheimer's disease (AD) and accumulating evidence suggests that fragmentation with a toxic-gain of function may be a key molecular step associated with this risk. Recently, we demonstrated strong immunoreactivity of a 151 amino-terminal fragment of apoE4 (E4-fragment) within the nucleus of microglia in the human AD brain. In vitro, this fragment led to toxicity and activation of inflammatory processes in BV2 microglia cells. Additionally, a transcriptome analysis following exogenous treatment of BV2 microglia cells with this E4 fragment led to a > 2-fold up regulation of 1,608 genes, with many genes playing a role in inflammation and microglia activation. To extend these findings, we here report a similar transcriptome analysis in BV2 microglia cells following treatment with full-length ApoE4 (FL-ApoE4). The results indicated that full-length ApoE4 had a very small effect on gene expression compared to the fragment. Only 48 differentially expressed genes (DEGs) were identified (p < 0.05, and greater than 2-fold change). A gene ontology analysis of these DEGs indicated that they are not involved in inflammatory and activation processes, in contrast to the genes up regulated by the E4-fragment. In addition, genes that showed a negative fold-change upon FL-E4 treatment typically showed a strong positive fold-change upon treatment with the fragment (Pearson's r = -0.7). Taken together, these results support the hypothesis that a key step in the conversion of microglia to an activated phenotype is proteolytic cleavage of FL-ApoE4. Therefore, the neutralization of this amino-terminal fragment of ApoE4, specifically, may serve as an important therapeutic strategy in the treatment of AD.
载脂蛋白E4 (APOE4)等位基因是迟发性阿尔茨海默病(AD)的最大危险因素，越来越多的证据表明，带有毒性功能获得的片段化可能是与这种风险相关的关键分子步骤。最近，我们证明了apoE4的151个氨基末端片段(e4片段)在人AD大脑的小胶质细胞核中具有很强的免疫反应性。在体外，该片段导致BV2小胶质细胞的毒性和炎症过程的激活。此外，用该E4片段外源处理BV2小胶质细胞后的转录组分析导致1608个基因的2倍以上上调，其中许多基因在炎症和小胶质细胞激活中发挥作用。为了扩展这些发现，我们在这里报告了用全长ApoE4 (FL-ApoE4)治疗后BV2小胶质细胞的类似转录组分析。结果表明，与片段相比，全长ApoE4对基因表达的影响很小。仅鉴定出48个差异表达基因(deg) (p < 0.05，变化大于2倍)。对这些deg的基因本体论分析表明，与e4片段上调的基因相反，它们不参与炎症和激活过程。此外，经FL-E4处理后表现为负折叠变化的基因通常在用该片段处理后表现为强烈的正折叠变化(Pearson’s r = -0.7)。综上所述，这些结果支持了小胶质细胞转化为活化表型的关键步骤是FL-ApoE4的蛋白水解裂解的假设。因此，具体地说，中和ApoE4的这个氨基末端片段可能是治疗AD的重要治疗策略。
{"title":"Fragmentation of Apolipoprotein E4 is Required for Differential Expression of Inflammation and Activation Related Genes in Microglia Cells.","authors":"Troy T Rohn, James D Beck, Stephanie J Galla, Noail F Isho, Tanner B Pollock, Tarun Suresh, Arni Kulkarni, Tanya Sanghal, Eric J Hayden","doi":"10.23937/2643-4539/1710020","DOIUrl":"https://doi.org/10.23937/2643-4539/1710020","url":null,"abstract":"<p><p>The apolipoprotein E4 (<i>APOE4</i>) allele represents the single greatest risk factor for late-onset Alzheimer's disease (AD) and accumulating evidence suggests that fragmentation with a toxic-gain of function may be a key molecular step associated with this risk. Recently, we demonstrated strong immunoreactivity of a 151 amino-terminal fragment of apoE4 (E4-fragment) within the nucleus of microglia in the human AD brain. In vitro, this fragment led to toxicity and activation of inflammatory processes in BV2 microglia cells. Additionally, a transcriptome analysis following exogenous treatment of BV2 microglia cells with this E4 fragment led to a > 2-fold up regulation of 1,608 genes, with many genes playing a role in inflammation and microglia activation. To extend these findings, we here report a similar transcriptome analysis in BV2 microglia cells following treatment with full-length ApoE4 (FL-ApoE4). The results indicated that full-length ApoE4 had a very small effect on gene expression compared to the fragment. Only 48 differentially expressed genes (DEGs) were identified (p < 0.05, and greater than 2-fold change). A gene ontology analysis of these DEGs indicated that they are not involved in inflammatory and activation processes, in contrast to the genes up regulated by the E4-fragment. In addition, genes that showed a negative fold-change upon FL-E4 treatment typically showed a strong positive fold-change upon treatment with the fragment (Pearson's r = -0.7). Taken together, these results support the hypothesis that a key step in the conversion of microglia to an activated phenotype is proteolytic cleavage of FL-ApoE4. Therefore, the neutralization of this amino-terminal fragment of ApoE4, specifically, may serve as an important therapeutic strategy in the treatment of AD.</p>","PeriodicalId":92384,"journal":{"name":"International journal of neurodegenerative disorders","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8529910/pdf/nihms-1745767.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39555575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: The patient was given the diagnosis during evaluation at a comprehensive amyotrophic lateral sclerosis (ALS) center by the neurology team. During the year prior to the diagnosis of ALS the patient was evaluated by seven different neurologists over the course of the progressive disease. Coordinated evaluation refined the diagnosis to cryoglobulinemia causing a vasculitis that resulted in severe peripheral neuropathy. Case presentation: An 86-year-old female in general good health with insidious onset of symptoms that gained her classification qualification for an assigned diagnosis of amyotrophic lateral sclerosis. As frequently associated with a devastating diagnosis the patient and family remained motivated for any additional helpful options. Conclusion: Presented here is how the patient went from bedbound to assisted ambulation along with the complex medical evaluation, case details, exam findings, and additional medical information that allowed and hindered the patient's ability to recover. ALS remains one of the most devastating diagnosis that a patient could be given and the additional information in this case could be helpful to other patients. Described below is the thought process of a coordinated effort when presented with a diagnosis of exclusion.
{"title":"Obtaining Clinical Improvement in Amyotrophic Lateral Sclerosis with Stabilization of Progressive Functional Loss: Case Report Presentation and Review","authors":"Orehek Allen J","doi":"10.36959/459/602","DOIUrl":"https://doi.org/10.36959/459/602","url":null,"abstract":"Background: The patient was given the diagnosis during evaluation at a comprehensive amyotrophic lateral sclerosis (ALS) center by the neurology team. During the year prior to the diagnosis of ALS the patient was evaluated by seven different neurologists over the course of the progressive disease. Coordinated evaluation refined the diagnosis to cryoglobulinemia causing a vasculitis that resulted in severe peripheral neuropathy. Case presentation: An 86-year-old female in general good health with insidious onset of symptoms that gained her classification qualification for an assigned diagnosis of amyotrophic lateral sclerosis. As frequently associated with a devastating diagnosis the patient and family remained motivated for any additional helpful options. Conclusion: Presented here is how the patient went from bedbound to assisted ambulation along with the complex medical evaluation, case details, exam findings, and additional medical information that allowed and hindered the patient's ability to recover. ALS remains one of the most devastating diagnosis that a patient could be given and the additional information in this case could be helpful to other patients. Described below is the thought process of a coordinated effort when presented with a diagnosis of exclusion.","PeriodicalId":92384,"journal":{"name":"International journal of neurodegenerative disorders","volume":"168 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72882889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abhayasinghe Kalpani, Dissanayake Lasith, S. Benjamin, C. Paul, Sumathipala Athula
Background: As a result of the global rise in life expectancy, dementia has become a major global health concern; it is considered to be one of the most burdensome conditions of later life. Despite 66% of older adults with dementia living in Low-and-Middle Income countries (LMIC), only 10% of dementia research has been conducted in these countries and more information is needed about research activity within LMIC to inform on global dementia research strategies. Todate no systematic reviews have been carried out to explore existing evidence of dementia research reported from Sri Lanka, despite it having the fastest ageing population in the region. Objective: To describe dementia research activity conducted in Sri Lanka. Method: Systematic searches of databases (MEDLINE, EMBASE, PsycINFO, AMED, CINAHL, SLJOL, Cochrane Library) and grey literature were conducted from each database inception to April 2020. Pre-defined inclusion and exclusion criteria were applied and papers were screened and quality assessed. Research activity by individual studies were mapped into four research domains. A narrative synthesis was conducted to describe dementia research activity. Findings and conclusions: Out of 971 papers retrieved from searches, 28 studies were included in the review. Results show evidence across four research domains; epidemiology (n = 6), pathophysiology (n = 4), screening for dementia (n = 13), and dementia management (n = 7). In comparison to the International Consortium for Health Outcome Measurement (ICHOM) standard set for dementia, this review found a lack of dementia research activity in Sri Lanka generally, as well as a lack of high-quality research, particularly in the areas of dementia prevalence, dementia care, characteristics of formal and informal caregivers, and service provision for people with dementia and their and families. There is a need for more high-quality research, with robust methodologies, which would inform policy and service provision in Sri Lanka for people with dementia.
{"title":"Dementia Research Activity in Sri Lanka: A Review","authors":"Abhayasinghe Kalpani, Dissanayake Lasith, S. Benjamin, C. Paul, Sumathipala Athula","doi":"10.36959/459/603","DOIUrl":"https://doi.org/10.36959/459/603","url":null,"abstract":"Background: As a result of the global rise in life expectancy, dementia has become a major global health concern; it is considered to be one of the most burdensome conditions of later life. Despite 66% of older adults with dementia living in Low-and-Middle Income countries (LMIC), only 10% of dementia research has been conducted in these countries and more information is needed about research activity within LMIC to inform on global dementia research strategies. Todate no systematic reviews have been carried out to explore existing evidence of dementia research reported from Sri Lanka, despite it having the fastest ageing population in the region. Objective: To describe dementia research activity conducted in Sri Lanka. Method: Systematic searches of databases (MEDLINE, EMBASE, PsycINFO, AMED, CINAHL, SLJOL, Cochrane Library) and grey literature were conducted from each database inception to April 2020. Pre-defined inclusion and exclusion criteria were applied and papers were screened and quality assessed. Research activity by individual studies were mapped into four research domains. A narrative synthesis was conducted to describe dementia research activity. Findings and conclusions: Out of 971 papers retrieved from searches, 28 studies were included in the review. Results show evidence across four research domains; epidemiology (n = 6), pathophysiology (n = 4), screening for dementia (n = 13), and dementia management (n = 7). In comparison to the International Consortium for Health Outcome Measurement (ICHOM) standard set for dementia, this review found a lack of dementia research activity in Sri Lanka generally, as well as a lack of high-quality research, particularly in the areas of dementia prevalence, dementia care, characteristics of formal and informal caregivers, and service provision for people with dementia and their and families. There is a need for more high-quality research, with robust methodologies, which would inform policy and service provision in Sri Lanka for people with dementia.","PeriodicalId":92384,"journal":{"name":"International journal of neurodegenerative disorders","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75006841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-01-01DOI: 10.23937/2643-4539/1710017
Chan Mike KS, Zocchi Michele, T. Dina, Kour Anam K, Rene Lau Cher, Moya Roni, Fah Michelle WB
The incidence of Multiple sclerosis disease is rapidly increasing worldwide, for instance, across Asia, the utmost growth was confirmed in Japan from 1,000 in 1980 to more than 20,000 people in 2019 [1]. The phenomenon of “Westernization” in Asian countries which includes a specific choice of food and lifestyle was related to the higher prevalence of MS in Asia’s population which almost supports new findings on the great influence of gut and its microbiota in people worldwide. The current conventional therapy helps to prolong the periods between attacks and relapses, but in fact, does not slow down the disease progression and impact on physical activities which eventually leads to disabilities. The development of a new approach and data is highly required with the opportunity to avoid immunity suppression. This review article shares information on the complex integrative approach of the management of MS cases with the application of immune-modulating peptides, mitochondria derived neural peptides, precursor stem cells, active specific immunotherapy therapy and diet. The results showed a regeneration effect, stable prolonged remission, a reversal of symptoms, reduction of side effects, high efficacy of reduction of MS lesions as well as safety of combination (ongoing and integrative) approach. RevieW ARTiCLe
{"title":"Immunomodulating, Neuroprotective and Regenerative Modalities in Multiple Sclerosis Management","authors":"Chan Mike KS, Zocchi Michele, T. Dina, Kour Anam K, Rene Lau Cher, Moya Roni, Fah Michelle WB","doi":"10.23937/2643-4539/1710017","DOIUrl":"https://doi.org/10.23937/2643-4539/1710017","url":null,"abstract":"The incidence of Multiple sclerosis disease is rapidly increasing worldwide, for instance, across Asia, the utmost growth was confirmed in Japan from 1,000 in 1980 to more than 20,000 people in 2019 [1]. The phenomenon of “Westernization” in Asian countries which includes a specific choice of food and lifestyle was related to the higher prevalence of MS in Asia’s population which almost supports new findings on the great influence of gut and its microbiota in people worldwide. The current conventional therapy helps to prolong the periods between attacks and relapses, but in fact, does not slow down the disease progression and impact on physical activities which eventually leads to disabilities. The development of a new approach and data is highly required with the opportunity to avoid immunity suppression. This review article shares information on the complex integrative approach of the management of MS cases with the application of immune-modulating peptides, mitochondria derived neural peptides, precursor stem cells, active specific immunotherapy therapy and diet. The results showed a regeneration effect, stable prolonged remission, a reversal of symptoms, reduction of side effects, high efficacy of reduction of MS lesions as well as safety of combination (ongoing and integrative) approach. RevieW ARTiCLe","PeriodicalId":92384,"journal":{"name":"International journal of neurodegenerative disorders","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68754613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-10-21DOI: 10.23937/2643-4539/1710013
Adebisi Muslimat Kehinde, Xuezhong Li, T. Ehianeta, Liuyi
Objective: To establish correlation between lifestyles, obesity and the risks of Parkinson’s disease (PD). To ascertain the effect of PD on Body mass index (BMI). Methods: Keyword used in searching for similar articles on PubMed were, Obesity, hyperlipidemia, Metabolic syndrome (MetS), Neurodegenerative disorders, Parkinson’s diseases (PD). Papers from 2014-2019 related were compiled. Cases at Zhenjiang First people’s hospital similar was compiled to draw conclusions. I evaluated the association between years of diagnosis (YOD) of PD and BMI for both male and female patients and compared to controlled groups. There was a statistically significance between YOD of PD and BMI. Conclusion: Meta-analysis showed that YOD is inversely proportional to BMI. REviEw ARTicLE
{"title":"Part Two: Habit and Customs, Obesity and Parkinson's Disease","authors":"Adebisi Muslimat Kehinde, Xuezhong Li, T. Ehianeta, Liuyi","doi":"10.23937/2643-4539/1710013","DOIUrl":"https://doi.org/10.23937/2643-4539/1710013","url":null,"abstract":"Objective: To establish correlation between lifestyles, obesity and the risks of Parkinson’s disease (PD). To ascertain the effect of PD on Body mass index (BMI). Methods: Keyword used in searching for similar articles on PubMed were, Obesity, hyperlipidemia, Metabolic syndrome (MetS), Neurodegenerative disorders, Parkinson’s diseases (PD). Papers from 2014-2019 related were compiled. Cases at Zhenjiang First people’s hospital similar was compiled to draw conclusions. I evaluated the association between years of diagnosis (YOD) of PD and BMI for both male and female patients and compared to controlled groups. There was a statistically significance between YOD of PD and BMI. Conclusion: Meta-analysis showed that YOD is inversely proportional to BMI. REviEw ARTicLE","PeriodicalId":92384,"journal":{"name":"International journal of neurodegenerative disorders","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47635131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-10-14DOI: 10.23937/2643-4539/1710012
Adebisi Muslimat Kehinde, T. Ehianeta, Salim Mzee Said Abdulraman, Liuyi, Mahmud Abdul Nazif, Kanton Aaron Gia, Mustapha Abdullateef Taiye
Objective: Currently Parkinson's disease is becoming more common among younger people of ages from 30-40 years. The incidence is higher among patients with higher BMI, some reports has it that Obesity is a risk factor for Parkinson’s disease while some reported that there is no relationship between obesity and Parkinson’s disease. Parkinson’s disease patient at the time of diagnosis has a above normal BMI but this goes below normal as the disease progresses. Therefore, it is important to explore the relationship between Parkinson’s disease and Obesity. Methods: 349 outpatients and inpatients with Parkinson's disease were selected from the people's Hospital affiliated to Jiangsu University from 2014.01 to 2018.12, and 64 inpatients with non-cerebrovascular disease in the same period were selected as the control group. According to HoehnYahr grade, Parkinson's patients were divided into early stage (1~2 grade), middle stage (2.5~3 grade) and late stage (4~5 grade). The height, weight, waist circumference, total cholesterol (TC), TG (TG), high density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured and recorded. The relationship between the severity of Parkinson's disease and blood lipid was evaluated. Results: BMI in patients with early Parkinson's disease was higher than that in patients with other diseases, but there was no significant difference. Blood lipids in patients with early Parkinson's disease were higher than those in normal control group and in patients with advanced Parkinson's disease. Conclusion: Obesity may increase the prevalence of Parkinson's disease, while Parkinson's may decrease the obesity index of patients with early Parkinson's disease.
{"title":"Obesity may Increase the Prevalence of Parkinson's Disease while Parkinson's may Reduce Obesity Index in Patients","authors":"Adebisi Muslimat Kehinde, T. Ehianeta, Salim Mzee Said Abdulraman, Liuyi, Mahmud Abdul Nazif, Kanton Aaron Gia, Mustapha Abdullateef Taiye","doi":"10.23937/2643-4539/1710012","DOIUrl":"https://doi.org/10.23937/2643-4539/1710012","url":null,"abstract":"Objective: Currently Parkinson's disease is becoming more common among younger people of ages from 30-40 years. The incidence is higher among patients with higher BMI, some reports has it that Obesity is a risk factor for Parkinson’s disease while some reported that there is no relationship between obesity and Parkinson’s disease. Parkinson’s disease patient at the time of diagnosis has a above normal BMI but this goes below normal as the disease progresses. Therefore, it is important to explore the relationship between Parkinson’s disease and Obesity. Methods: 349 outpatients and inpatients with Parkinson's disease were selected from the people's Hospital affiliated to Jiangsu University from 2014.01 to 2018.12, and 64 inpatients with non-cerebrovascular disease in the same period were selected as the control group. According to HoehnYahr grade, Parkinson's patients were divided into early stage (1~2 grade), middle stage (2.5~3 grade) and late stage (4~5 grade). The height, weight, waist circumference, total cholesterol (TC), TG (TG), high density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured and recorded. The relationship between the severity of Parkinson's disease and blood lipid was evaluated. Results: BMI in patients with early Parkinson's disease was higher than that in patients with other diseases, but there was no significant difference. Blood lipids in patients with early Parkinson's disease were higher than those in normal control group and in patients with advanced Parkinson's disease. Conclusion: Obesity may increase the prevalence of Parkinson's disease, while Parkinson's may decrease the obesity index of patients with early Parkinson's disease.","PeriodicalId":92384,"journal":{"name":"International journal of neurodegenerative disorders","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49489240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-18DOI: 10.23937/2643-4539/1710010
K. Deeksha., N. Abhishek
Alzheimer is one of the most common causes of dementia that influence nerve cells in various parts of the brain. Pathologically it is caused because of intracellular neurofibrillary tangles and extracellular amyloidal protein and results in the deposition of plaques which obstruct the communication between the nerve cells resulting in this neurodegenerative disease. The genetic risk factor found to be associated with this disease is mutation in APP, PSEN1 and PSEN2 genes. Also, the diet and nutrition play quite an important role in the development as well as prevention of Alzheimer Disease. The biomarker used for the detection of the disease should be able to differentiate between different causes of dementia and should be able to detect it at early stage. Further the use of Induced pluripotent stem cells has proven to be an effective treatment for the cure of this disease. The objective of this review is to highlight about the pathway that lead to this disease and stem cell treatment of this disease.
{"title":"A Review on Alzheimer Disease","authors":"K. Deeksha., N. Abhishek","doi":"10.23937/2643-4539/1710010","DOIUrl":"https://doi.org/10.23937/2643-4539/1710010","url":null,"abstract":"Alzheimer is one of the most common causes of dementia that influence nerve cells in various parts of the brain. Pathologically it is caused because of intracellular neurofibrillary tangles and extracellular amyloidal protein and results in the deposition of plaques which obstruct the communication between the nerve cells resulting in this neurodegenerative disease. The genetic risk factor found to be associated with this disease is mutation in APP, PSEN1 and PSEN2 genes. Also, the diet and nutrition play quite an important role in the development as well as prevention of Alzheimer Disease. The biomarker used for the detection of the disease should be able to differentiate between different causes of dementia and should be able to detect it at early stage. Further the use of Induced pluripotent stem cells has proven to be an effective treatment for the cure of this disease. The objective of this review is to highlight about the pathway that lead to this disease and stem cell treatment of this disease.","PeriodicalId":92384,"journal":{"name":"International journal of neurodegenerative disorders","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41595382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-18DOI: 10.23937/2643-4539/1710011
E. Nilufer, S. Rakhi, P MalleisJames, Dore-Duffy Paula
The mammalian brain depends on a continuous supply of oxygen and glucose to meet metabolic demand. Adaptive mechanisms allow brain cells to exist under conditions of moderately low oxygen when ‘idling’ or exposure to high altitude as well as elevated oxygen delivery when activated. Regulation involves numerous intrinsic and extrinsic adaptive mechanisms that serve to maintain metabolic homeostasis. Under conditions of chronic low oxygen (10%) endogenous changes in CNS angiodynamics help promote survival. We questioned whether endogenous adaptation to a stressor such as mild changes in respiratory oxygen altered chronic inflammation in an animal model of multiple sclerosis (MS) experimental autoimmune encephalomyelitis (EAE). We previously reported that when mice were exposed to chronic mild hypoxia at the time of immunization with myelin oligodendrocyte glycoprotein (MOG) they exhibited a delay in disease onset and a decrease in disease severity. Changes in clinical EAE were associated with decreased T cell infiltration into the spinal cord as well as altered regulatory T-cell subsets. In this study, we examine the effect of in vivo exposure to chronic mild hypoxia after the development of disease symptoms. Mice were exposed to 10% normobaric oxygen after the clinical symptoms reach to score 2. Exposure to mild hypoxia ameliorated chronic inflammatory activity and was associated with reduction in clinical score. Further we found evidence that exposure to hypoxia increased the ratio of Foxp3+ Tregs and IL-10+ and Blimp1+ T cells following exposure to low oxygen. In addition, chronic low oxygen decreased evidence of endothelial activation.
{"title":"Endogenous Adaptation to Chronic Mild Hypoxia Shifts the Balance towards Anti-Inflammatory Milieu in Progressive Myelin Oligodendrocyte Glycoprotein Induced EAE","authors":"E. Nilufer, S. Rakhi, P MalleisJames, Dore-Duffy Paula","doi":"10.23937/2643-4539/1710011","DOIUrl":"https://doi.org/10.23937/2643-4539/1710011","url":null,"abstract":"The mammalian brain depends on a continuous supply of oxygen and glucose to meet metabolic demand. Adaptive mechanisms allow brain cells to exist under conditions of moderately low oxygen when ‘idling’ or exposure to high altitude as well as elevated oxygen delivery when activated. Regulation involves numerous intrinsic and extrinsic adaptive mechanisms that serve to maintain metabolic homeostasis. Under conditions of chronic low oxygen (10%) endogenous changes in CNS angiodynamics help promote survival. We questioned whether endogenous adaptation to a stressor such as mild changes in respiratory oxygen altered chronic inflammation in an animal model of multiple sclerosis (MS) experimental autoimmune encephalomyelitis (EAE). We previously reported that when mice were exposed to chronic mild hypoxia at the time of immunization with myelin oligodendrocyte glycoprotein (MOG) they exhibited a delay in disease onset and a decrease in disease severity. Changes in clinical EAE were associated with decreased T cell infiltration into the spinal cord as well as altered regulatory T-cell subsets. In this study, we examine the effect of in vivo exposure to chronic mild hypoxia after the development of disease symptoms. Mice were exposed to 10% normobaric oxygen after the clinical symptoms reach to score 2. Exposure to mild hypoxia ameliorated chronic inflammatory activity and was associated with reduction in clinical score. Further we found evidence that exposure to hypoxia increased the ratio of Foxp3+ Tregs and IL-10+ and Blimp1+ T cells following exposure to low oxygen. In addition, chronic low oxygen decreased evidence of endothelial activation.","PeriodicalId":92384,"journal":{"name":"International journal of neurodegenerative disorders","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42080219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-08-01DOI: 10.23937/2643-4539/1710009
Jordan Elliott-King, E. Peel, E. Hogervorst
Background: Physical activity has the potential to improve cognition for those with dementia, as demonstrated by randomised controlled trials lasting at least 6 weeks. Research is yet to explore the acute cognitive effects of physical activity for people with dementia. Acute resistance physical activity with healthy late-middle aged individuals has been shown to facilitate general cognition, as well as benefit executive function specifically. This study therefore aimed to establish if people with dementia experience cognitive benefits from acute resistance physical activity over and above a social control.Methods: A cross-sectional study design was applied to compare resistance physical activity to bingo between 10 participants with dementia to 15 age-matched controls. Following University ethical approval, participants were recruited from Alzheimer’s or dementia activity and support groups held in the community. Acute cognitive effects were assessed using the Mini Mental Status Examination (MMSE), Hopkins Verbal Learning Test (HVLT), Verbal Fluency (VF) and The Cognitive Computerised Test Battery for Individual’s with Intellectual Disabilities (CCIID); before and after a short bout of seated resistance band physical activity or a social control, bingo. The participants then completed the opposing activity 6 weeks later, and then cognitive assessments alone a further 6 weeks later. This allowed to analyse cognitive effects immediately and 6 weeks after. Statistical analysis included Mann Whitney U test, Chi-square test and Mix-measured ANOVA to compare scores across time-points.Results: Participants had a mean age of 76 years, 40% were male and 60% were female. For participants with dementia immediately after the resistance band activity improvements can be observed on the MMSE, VF, HVLT, Series, Jigsaw and Total CCIID. Only the MMSE, Series and Total CCIID still showed improvements at 6-week follow-up. Immediately following the psychosocial intervention, participants with dementia only showed improvements on the HVLT, which were not sustained after 6-weeks. For age-matched controls, bingo appeared to be more beneficial than physical activity.Conclusion: These results indicate that there are differential acute effects of activity depending upon pre-existing cognitive ability. Specific cognitive benefits may be available for people with dementia following resistance band physical activity. This pilot study shows promising indications for physical activity as a therapy for dementia, however results should be interpreted with caution due to the small sample size of this study.
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