Pub Date : 2017-06-20DOI: 10.4172/2161-0460.1000337
C. Swart, Akile Khoza, K. Khan, S. G. L. Roux, A. Plessis, B. Loos
Objective: Autophagic maintenance of protein turnover for neuronal homeostasis is of critical importance. Although autophagy dysfunction contributes to neurodegenerative pathology, it remains unclear why certain brain regions are initially targeted compared to others. In Alzheimer's disease, the hippocampus appears to be most severely and initially affected compared to regions such as the cerebellum, which seem to be spared initially and are only targeted during later stages of neurodegeneration. Here we hypothesize that brain-region specific variations in basal autophagic activity may underlie sensitivity to proteotoxicity and contribute towards pathology. We investigated the abundance of key autophagic markers in different regions of the mouse brain to determine whether variations in basal autophagic activity may underlie brain-region susceptibility to neurodegeneration. Methods: Autophagic lysosomal degradation was inhibited using chloroquine in vivo and bafilomycin ex vivo. We investigated the accumulation of LC3-II and p62 protein levels in different regions of the mouse brain following inhibition using western blot analysis, immunofluorescence and micro-computed tomography imaging techniques. Results: Results indicate clear and robust variation of autophagic marker abundance between different regions of the mouse brain, both in our in vivo and ex vivo models. Increased protein levels were particularly observed in the cerebellum compared to the hippocampus region, suggesting distinct and region specific changes in autophagic activity. Conclusion: Functional specificity and metabolic demands of different brain regions may translate into differential autophagic activities, which may vary from one region to the next. Here we report regional variations of key autophagic markers between different regions of the mouse brain when autophagosome degradation was inhibited. These findings indicate enhanced basal autophagic activity in the cerebellum compared to the hippocampus. We therefore conclude that enhanced basal autophagic activity may render certain brain regions better equipped to deal with imbalances in protein degradation and that lower levels of basal autophagic activity may underlie regional susceptibility towards pathological decline.
{"title":"Investigating Basal Autophagic Activity in Brain Regions Associated with Neurodegeneration using In Vivo and Ex Vivo Models","authors":"C. Swart, Akile Khoza, K. Khan, S. G. L. Roux, A. Plessis, B. Loos","doi":"10.4172/2161-0460.1000337","DOIUrl":"https://doi.org/10.4172/2161-0460.1000337","url":null,"abstract":"Objective: Autophagic maintenance of protein turnover for neuronal homeostasis is of critical importance. Although autophagy dysfunction contributes to neurodegenerative pathology, it remains unclear why certain brain regions are initially targeted compared to others. In Alzheimer's disease, the hippocampus appears to be most severely and initially affected compared to regions such as the cerebellum, which seem to be spared initially and are only targeted during later stages of neurodegeneration. Here we hypothesize that brain-region specific variations in basal autophagic activity may underlie sensitivity to proteotoxicity and contribute towards pathology. We investigated the abundance of key autophagic markers in different regions of the mouse brain to determine whether variations in basal autophagic activity may underlie brain-region susceptibility to neurodegeneration. Methods: Autophagic lysosomal degradation was inhibited using chloroquine in vivo and bafilomycin ex vivo. We investigated the accumulation of LC3-II and p62 protein levels in different regions of the mouse brain following inhibition using western blot analysis, immunofluorescence and micro-computed tomography imaging techniques. Results: Results indicate clear and robust variation of autophagic marker abundance between different regions of the mouse brain, both in our in vivo and ex vivo models. Increased protein levels were particularly observed in the cerebellum compared to the hippocampus region, suggesting distinct and region specific changes in autophagic activity. Conclusion: Functional specificity and metabolic demands of different brain regions may translate into differential autophagic activities, which may vary from one region to the next. Here we report regional variations of key autophagic markers between different regions of the mouse brain when autophagosome degradation was inhibited. These findings indicate enhanced basal autophagic activity in the cerebellum compared to the hippocampus. We therefore conclude that enhanced basal autophagic activity may render certain brain regions better equipped to deal with imbalances in protein degradation and that lower levels of basal autophagic activity may underlie regional susceptibility towards pathological decline.","PeriodicalId":15012,"journal":{"name":"Journal of Alzheimers Disease & Parkinsonism","volume":"46 1","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2017-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84431334","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 : 2017-06-20DOI: 10.4172/2161-0460.1000335
M. Marano, S. Migliore, Sabrina Maffi, F. Consoli, A. Luca, Irene Mazzante, F. Squitieri
Objective: Huntington disease (HD) generally manifests in adulthood. Large mutations with CAG repeat expansion in HTT gene may rarely cause juvenile Huntington disease (JHD) in early childhood or adolescence with atypical clinical features, i.e., atypical parkinsonism, if compared to adult patients. Our objective is to characterize the rare occurrence of clinical manifestations in children carrying mutations in the low-mild size, generally causing adult HD with typical choreic movements. Methods: We are following up a subgroup of young subjects with HD mutation who manifested with disabling psychiatric condition since early childhood or adolescence. We are collecting data by the observational studies Registry and ENROLL-HD since 2004. Among 60 JHD patients we are currently following-up, we selected people who carry a mutation in the mild range of CAG expansions (i.e., expected to manifest in adulthood), psychiatric manifestations and no neurological signs or movement disorders suggestive of HD. All patients were genetically (i.e., CAG size analysis) and clinically (i.e., total motor score within the Unified HD Rating Scale) characterized. Results: We found four subjects who showed the characteristics for this analysis. All four subjects presented a CAG expansion size <45 repeats. Two patients manifested a schizophrenia-like disturbance during their adolescence, with the later appearance of motor signs after age 20. In the other two cases, patients presented symptoms of autistic spectrum disorder, since infancy. One of them showed also a schizophrenia-like disturbance and, later, HD onset with motor signs after 20. A 45 year old patient is currently manifesting an autistic disorder in absence of others neurological signs. Conclusion: The description of JHD includes sometimes children with psychiatric manifestations associated with adult motor onset. We advise to pay careful attention to such rare conditions that might represent either psychiatric conditions erroneously classified as JHD or prodromic adult HD cases.
{"title":"Children with Mild CAG Repeat Expansion in HTT Gene Showing Psychiatric but not Neurological Presentation: Is It One More Shade of Huntington Disease?","authors":"M. Marano, S. Migliore, Sabrina Maffi, F. Consoli, A. Luca, Irene Mazzante, F. Squitieri","doi":"10.4172/2161-0460.1000335","DOIUrl":"https://doi.org/10.4172/2161-0460.1000335","url":null,"abstract":"Objective: Huntington disease (HD) generally manifests in adulthood. Large mutations with CAG repeat expansion in HTT gene may rarely cause juvenile Huntington disease (JHD) in early childhood or adolescence with atypical clinical features, i.e., atypical parkinsonism, if compared to adult patients. Our objective is to characterize the rare occurrence of clinical manifestations in children carrying mutations in the low-mild size, generally causing adult HD with typical choreic movements. Methods: We are following up a subgroup of young subjects with HD mutation who manifested with disabling psychiatric condition since early childhood or adolescence. We are collecting data by the observational studies Registry and ENROLL-HD since 2004. Among 60 JHD patients we are currently following-up, we selected people who carry a mutation in the mild range of CAG expansions (i.e., expected to manifest in adulthood), psychiatric manifestations and no neurological signs or movement disorders suggestive of HD. All patients were genetically (i.e., CAG size analysis) and clinically (i.e., total motor score within the Unified HD Rating Scale) characterized. Results: We found four subjects who showed the characteristics for this analysis. All four subjects presented a CAG expansion size <45 repeats. Two patients manifested a schizophrenia-like disturbance during their adolescence, with the later appearance of motor signs after age 20. In the other two cases, patients presented symptoms of autistic spectrum disorder, since infancy. One of them showed also a schizophrenia-like disturbance and, later, HD onset with motor signs after 20. A 45 year old patient is currently manifesting an autistic disorder in absence of others neurological signs. Conclusion: The description of JHD includes sometimes children with psychiatric manifestations associated with adult motor onset. We advise to pay careful attention to such rare conditions that might represent either psychiatric conditions erroneously classified as JHD or prodromic adult HD cases.","PeriodicalId":15012,"journal":{"name":"Journal of Alzheimers Disease & Parkinsonism","volume":"35 1","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2017-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72810477","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 : 2017-06-07DOI: 10.4172/2161-0460.1000332
Saima Zafar, N. Younas, I. Zerr
Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare but fatal type of spongiform encephalopathy with unidentified origin. The conjoining methionine-valine polymorphism of PRNP gene at codon 129 and two types of prion protein (PrPsc types 1 and 2) described the six different molecular subtypes (MM1, MM2, MV1, MV2, VV1 and VV2) of sCJD. Presumptive subtype specific diagnosis showed differential clinical manifestations and levels of CSF 14-3-3 protein. Even with the above mentioned differential diagnostic guidelines, pre-mortem subtype specific diagnosis of sCJD can be unreliable with high rates of misdiagnosis. The need for more reliable biomarkers for improving the diagnosis as well as understanding the pathogenesis of this mysterious ailment is amplified. This review compiles the levels of CSF proteins, i.e., PrPC, PrPSC 14-3-3, tau, phosphorylated tau, S100B, neuron-specific enolase (NSE) alpha-synuclein and beta-amyloid to differential diagnosis subtype specific sCJD cases. The detection of pre-mortem distinction targets might be useful diagnostic tool for sCJD in subtype specific manner and might lead towards differential treatment approaches.
{"title":"Subtype Specific CSF Biomarkers in Sporadic Creutzfeldt-Jakob Disease","authors":"Saima Zafar, N. Younas, I. Zerr","doi":"10.4172/2161-0460.1000332","DOIUrl":"https://doi.org/10.4172/2161-0460.1000332","url":null,"abstract":"Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare but fatal type of spongiform encephalopathy with unidentified origin. The conjoining methionine-valine polymorphism of PRNP gene at codon 129 and two types of prion protein (PrPsc types 1 and 2) described the six different molecular subtypes (MM1, MM2, MV1, MV2, VV1 and VV2) of sCJD. Presumptive subtype specific diagnosis showed differential clinical manifestations and levels of CSF 14-3-3 protein. Even with the above mentioned differential diagnostic guidelines, pre-mortem subtype specific diagnosis of sCJD can be unreliable with high rates of misdiagnosis. The need for more reliable biomarkers for improving the diagnosis as well as understanding the pathogenesis of this mysterious ailment is amplified. This review compiles the levels of CSF proteins, i.e., PrPC, PrPSC 14-3-3, tau, phosphorylated tau, S100B, neuron-specific enolase (NSE) alpha-synuclein and beta-amyloid to differential diagnosis subtype specific sCJD cases. The detection of pre-mortem distinction targets might be useful diagnostic tool for sCJD in subtype specific manner and might lead towards differential treatment approaches.","PeriodicalId":15012,"journal":{"name":"Journal of Alzheimers Disease & Parkinsonism","volume":"182 1","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2017-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80342549","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 : 2017-06-05DOI: 10.4172/2161-0460.1000331
J. Gronewold, D. Hermann
In ageing populations, chronic kidney disease (CKD) gets an increasing health problem worldwide. While current therapy of CKD mostly focusses on kidney function and cardiovascular comorbidity, cognition, which crucially influences adherence to CKD therapy, is often neglected. Prevalence of cognitive impairment is high in CKD, ranging from 17% to 87%, depending on CKD severity and cognitive domain affected. In contrast to Alzheimer’s disease patients, which often show impairment in memory function, CKD patients present with a broader spectrum of cognitive deficits, namely impairment in executive function, information processing, language and visuoconstruction which is usually mild in early CKD stages but advances with CKD progression and progression of comorbidities. Mechanisms underlying cognitive impairment in CKD are discussed and conclusions are derived how cognitive impairment may be prevented in CKD and, if cognitive deficits are present, how cognitive impairment may be taken into consideration in patient management.
{"title":"Cognitive Impairment in Chronic Kidney Disease-Prevalence, Mechanisms and Consequences","authors":"J. Gronewold, D. Hermann","doi":"10.4172/2161-0460.1000331","DOIUrl":"https://doi.org/10.4172/2161-0460.1000331","url":null,"abstract":"In ageing populations, chronic kidney disease (CKD) gets an increasing health problem worldwide. While current therapy of CKD mostly focusses on kidney function and cardiovascular comorbidity, cognition, which crucially influences adherence to CKD therapy, is often neglected. Prevalence of cognitive impairment is high in CKD, ranging from 17% to 87%, depending on CKD severity and cognitive domain affected. In contrast to Alzheimer’s disease patients, which often show impairment in memory function, CKD patients present with a broader spectrum of cognitive deficits, namely impairment in executive function, information processing, language and visuoconstruction which is usually mild in early CKD stages but advances with CKD progression and progression of comorbidities. Mechanisms underlying cognitive impairment in CKD are discussed and conclusions are derived how cognitive impairment may be prevented in CKD and, if cognitive deficits are present, how cognitive impairment may be taken into consideration in patient management.","PeriodicalId":15012,"journal":{"name":"Journal of Alzheimers Disease & Parkinsonism","volume":"7 1","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2017-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78644408","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 : 2017-06-02DOI: 10.4172/2161-0460.1000330
Chongfeng-Bi, Hairong-Qian
Multiple system atrophy (MSA) is a sporadic neurodegenerative disease among adults, which can be characterized by autonomic nerve dysfunction, Parkinsonism, ataxia and pyramidal tract dysfunction, or overlapped symptoms. It can mainly be divided into two types: Parkinsonism (MSA-P) and cerebellum type (MSA-C). The pathology of this disease is the accumulation of alpha-synuclein in oligodendrocyte. And because of this, it belongs to synucleinopathies. Alpha-synuclein is a kind of protein, which has a close connection with lipid membrane in the process of biosynthesis of central nervous system, and this close relationship may play a crucial role in the mechanism of alpha-synucleinopathies. Recently researchers who have focused on the serum lipids level in MSA patients are taking a stab at finding the diagnostic biomarkers, like serum cholesterol level, so as to develop effective therapies in the early stage of MSA. Therefore, the purpose of our review is to summarize the valuable part of recent researches on cholesterol level of MSA patients and to discuss the optimal way to evaluate MSA disease in a simple way to diagnose it early.
多系统萎缩(Multiple system atrophy, MSA)是一种散发性成人神经退行性疾病，以自主神经功能障碍、帕金森病、共济失调、锥体束功能障碍或症状重叠为特征。主要分为帕金森型(MSA-P)和小脑型(MSA-C)两种。这种疾病的病理是α -突触核蛋白在少突胶质细胞中的积累。正因为如此，它属于突触核蛋白病。α -突触核蛋白是中枢神经系统生物合成过程中与脂膜密切相关的一种蛋白，这种密切关系可能在α -突触核蛋白病的发生机制中起着至关重要的作用。最近，关注MSA患者血脂水平的研究人员正在尝试寻找诊断性生物标志物，如血清胆固醇水平，以便在MSA早期开发有效的治疗方法。因此，我们的目的是总结最近关于MSA患者胆固醇水平的研究中有价值的部分，并讨论如何评估MSA疾病，简单早期诊断的最佳方法。
{"title":"Cholesterol Homeostasis and the Pathogenesis of Multiple System Atrophy","authors":"Chongfeng-Bi, Hairong-Qian","doi":"10.4172/2161-0460.1000330","DOIUrl":"https://doi.org/10.4172/2161-0460.1000330","url":null,"abstract":"Multiple system atrophy (MSA) is a sporadic neurodegenerative disease among adults, which can be characterized by autonomic nerve dysfunction, Parkinsonism, ataxia and pyramidal tract dysfunction, or overlapped symptoms. It can mainly be divided into two types: Parkinsonism (MSA-P) and cerebellum type (MSA-C). The pathology of this disease is the accumulation of alpha-synuclein in oligodendrocyte. And because of this, it belongs to synucleinopathies. Alpha-synuclein is a kind of protein, which has a close connection with lipid membrane in the process of biosynthesis of central nervous system, and this close relationship may play a crucial role in the mechanism of alpha-synucleinopathies. Recently researchers who have focused on the serum lipids level in MSA patients are taking a stab at finding the diagnostic biomarkers, like serum cholesterol level, so as to develop effective therapies in the early stage of MSA. Therefore, the purpose of our review is to summarize the valuable part of recent researches on cholesterol level of MSA patients and to discuss the optimal way to evaluate MSA disease in a simple way to diagnose it early.","PeriodicalId":15012,"journal":{"name":"Journal of Alzheimers Disease & Parkinsonism","volume":"19 1","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2017-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85186693","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 : 2017-05-29DOI: 10.4172/2161-0460.1000329
Arvio Maria, Bjelogrlic-Laakso Nina
Background: Alzheimer’s disease is the most common cause of death in people who have Down syndrome. This prospective, population-based, 15-year follow-up study aimed to define the onset age of dementia. Methods: At baseline 98 adults were screened for the first time by using the Present Psychiatric State-Learning Disabilities assessment. These screenings were repeated twice more during the study. Results: The indicative signs for dementia increased rapidly after the age of 35 and appeared most frequently as reduced self-care skills, loss of energy, impaired understanding and forgetfulness. Conclusion: Regular follow-up of people who have Down syndrome from the age of 30 onward enables appropriate interventions to delay the progression of dementia.
{"title":"Down Syndrome - Onset Age of Dementia","authors":"Arvio Maria, Bjelogrlic-Laakso Nina","doi":"10.4172/2161-0460.1000329","DOIUrl":"https://doi.org/10.4172/2161-0460.1000329","url":null,"abstract":"Background: Alzheimer’s disease is the most common cause of death in people who have Down syndrome. This prospective, population-based, 15-year follow-up study aimed to define the onset age of dementia. Methods: At baseline 98 adults were screened for the first time by using the Present Psychiatric State-Learning Disabilities assessment. These screenings were repeated twice more during the study. Results: The indicative signs for dementia increased rapidly after the age of 35 and appeared most frequently as reduced self-care skills, loss of energy, impaired understanding and forgetfulness. Conclusion: Regular follow-up of people who have Down syndrome from the age of 30 onward enables appropriate interventions to delay the progression of dementia.","PeriodicalId":15012,"journal":{"name":"Journal of Alzheimers Disease & Parkinsonism","volume":"63 1","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2017-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84924984","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 : 2017-05-22DOI: 10.4172/2161-0460.1000326
H. Okamoto
Japanese traditional medicine (Kampo) was the main medical treatment in Japan from the 6th century until Western medicine was introduced from Europe several hundred years ago, and it had been developed to treat all kinds of human diseases. Recently, Kampo has received renewed attention because it provides a valid alternative for treating symptoms refractory to modern conventional medicine. Some Kampo formulas have accumulated clinical evidence for their effectiveness, especially in postoperative bowel dysfunction, functional dyspepsia, and dementia. This article reviews clinical studies showing evidence for the efficacy of Kampo formulas in treating dementia-related symptoms.
{"title":"Treatment of Dementia-related Symptoms with Japanese Traditional Medicine (Kampo): A Review of Clinical Studies","authors":"H. Okamoto","doi":"10.4172/2161-0460.1000326","DOIUrl":"https://doi.org/10.4172/2161-0460.1000326","url":null,"abstract":"Japanese traditional medicine (Kampo) was the main medical treatment in Japan from the 6th century until Western medicine was introduced from Europe several hundred years ago, and it had been developed to treat all kinds of human diseases. Recently, Kampo has received renewed attention because it provides a valid alternative for treating symptoms refractory to modern conventional medicine. Some Kampo formulas have accumulated clinical evidence for their effectiveness, especially in postoperative bowel dysfunction, functional dyspepsia, and dementia. This article reviews clinical studies showing evidence for the efficacy of Kampo formulas in treating dementia-related symptoms.","PeriodicalId":15012,"journal":{"name":"Journal of Alzheimers Disease & Parkinsonism","volume":"60 1","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2017-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79570154","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 : 2017-05-10DOI: 10.4172/2161-0460.1000323
Shovit Ranjan, K. Sharma
The key pathological changes associated with AD brain tissue are the accumulation of intracellular neurofibrillary tangles (NFTs) and abnormally aggregated ‘reactive’ proteins like β amyloid (Aβ) plaques and tau [3]. Several elements, such as senile plaques, neurofibrillary tangles (NFTs), abnormally aggregated ‘reactive’ proteins like β amyloid (Aβ) and tau, brain inflammation and exposure to aluminum has already shown the development of AD [4]. Brain derived neurotrophic factor (BDNF) gene is supposed to be one of the important genes, playing a significant role in AD progression [5,6]. However, as a complex disorder, the neuropathological etiology of AD mentioned above are not due to the gene itself, but are also supposed to be associated with the combined interaction between genes and environmental factors.
{"title":"Association of Brain-Derived Neurotrophic Factor (BDNF) Gene Snps G196A and C270T with Alzheimer’s Disease: A Meta-Analysis","authors":"Shovit Ranjan, K. Sharma","doi":"10.4172/2161-0460.1000323","DOIUrl":"https://doi.org/10.4172/2161-0460.1000323","url":null,"abstract":"The key pathological changes associated with AD brain tissue are the accumulation of intracellular neurofibrillary tangles (NFTs) and abnormally aggregated ‘reactive’ proteins like β amyloid (Aβ) plaques and tau [3]. Several elements, such as senile plaques, neurofibrillary tangles (NFTs), abnormally aggregated ‘reactive’ proteins like β amyloid (Aβ) and tau, brain inflammation and exposure to aluminum has already shown the development of AD [4]. Brain derived neurotrophic factor (BDNF) gene is supposed to be one of the important genes, playing a significant role in AD progression [5,6]. However, as a complex disorder, the neuropathological etiology of AD mentioned above are not due to the gene itself, but are also supposed to be associated with the combined interaction between genes and environmental factors.","PeriodicalId":15012,"journal":{"name":"Journal of Alzheimers Disease & Parkinsonism","volume":"39 1","pages":"1-17"},"PeriodicalIF":0.0,"publicationDate":"2017-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80936811","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 : 2017-04-30DOI: 10.4172/2161-0460.1000321
Ewa PapuÄ, K. Rejdak
Although Alzheimer’s disease (AD) has been mainly considered as a grey matter disorder, there is emerging evidence that myelin impairment may play an important role in AD pathology. These data come from animal neuropathological studies, but also from human pathological, biochemical and brain MRI studies. Classical neuropathological changes in AD such as the accumulation of aggregated As 42 and the presence of neurofibrillary tangles are responsible for neuronall loss, but they may also induce death of oligodendrocytes and myelin impairment. Accelerated deposition of As in brains of AD patients induces damage to oligodendrocytes and results in impaired myelin production. What is more interesting, there is also evidence that myelin pathology may precede As and tau pathologies in AD. Recent studies suggest that As and tau proteins may be by-products of myelin repair in AD, instead of being the primary underlying cause of dementia. This seems possible, considering the fact that attempts to control clinical symtomps of AD by removing As from the human brain have been unsuccesful. In this article, current knowledge on the place of myelin in AD pathology and its interactions with As and tau pathology is reviewed.
{"title":"Does Myelin Play the Leading Role in AlzheimerâÂÂs Disease Pathology?","authors":"Ewa PapuÄ, K. Rejdak","doi":"10.4172/2161-0460.1000321","DOIUrl":"https://doi.org/10.4172/2161-0460.1000321","url":null,"abstract":"Although Alzheimer’s disease (AD) has been mainly considered as a grey matter disorder, there is emerging evidence that myelin impairment may play an important role in AD pathology. These data come from animal neuropathological studies, but also from human pathological, biochemical and brain MRI studies. Classical neuropathological changes in AD such as the accumulation of aggregated As 42 and the presence of neurofibrillary tangles are responsible for neuronall loss, but they may also induce death of oligodendrocytes and myelin impairment. Accelerated deposition of As in brains of AD patients induces damage to oligodendrocytes and results in impaired myelin production. What is more interesting, there is also evidence that myelin pathology may precede As and tau pathologies in AD. Recent studies suggest that As and tau proteins may be by-products of myelin repair in AD, instead of being the primary underlying cause of dementia. This seems possible, considering the fact that attempts to control clinical symtomps of AD by removing As from the human brain have been unsuccesful. In this article, current knowledge on the place of myelin in AD pathology and its interactions with As and tau pathology is reviewed.","PeriodicalId":15012,"journal":{"name":"Journal of Alzheimers Disease & Parkinsonism","volume":"22 1","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2017-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90538693","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}
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