Neurodegenerative Diseases最新文献_第10页

Contents Vol. 20, 2020 目录2020年第20卷

IF 3 4区医学

Neurodegenerative Diseases Pub Date : 2020-01-01 DOI: 10.1159/000519819

引用次数: 0

Elevated Levels of Homocysteinesulfinic Acid in the Plasma of Patients with Amyotrophic Lateral Sclerosis: A Potential Source of Excitotoxicity? 肌萎缩性侧索硬化症患者血浆中同型半胱氨酸磺酸水平升高:兴奋性毒性的潜在来源?

IF 3 4区医学

Neurodegenerative Diseases Pub Date : 2020-01-01 Epub Date: 2021-06-21 DOI: 10.1159/000517964

Aven Lee, Buddhika Jayakody Arachchige, Robert Henderson, James Aylward, Pamela Ann McCombe

{"title":"Elevated Levels of Homocysteinesulfinic Acid in the Plasma of Patients with Amyotrophic Lateral Sclerosis: A Potential Source of Excitotoxicity?","authors":"Aven Lee, Buddhika Jayakody Arachchige, Robert Henderson, James Aylward, Pamela Ann McCombe","doi":"10.1159/000517964","DOIUrl":"https://doi.org/10.1159/000517964","url":null,"abstract":"Objectives: Excitotoxicity is thought to be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). One possible source of excitotoxicity is the presence of sulphur amino acids (SAAs). In the brain of subjects with ALS, there are increased levels of taurine. In the metabolism of methionine to taurine, excitatory sulphur amino acids (SAAs) are formed. These could potentially contribute to excitotoxicity in ALS. The present study has examined whether plasma levels of SAAs in 38 ALS patients differ from those of 30 healthy controls.Methods: Plasma levels of SAAs were measured by liquid chromatography mass spectrometry.Results: There were no significant changes in plasma cysteic acid, cysteine sulfinic acid, and homocysteic acid in ALS patients compared to healthy subjects. Significant elevations in plasma homocysteinesulfinic acid (HCSA) levels (p < 0.0001) were observed in the ALS patients (75.91 ± 15.38 nM) compared to healthy controls (54.06 ± 8.503 nM); 50% of the ALS patients had HCSA levels that were 1.5-2-folds higher than those of controls. Plasma levels of HCSA differed significantly (p = 0.0440) between patients with bulbar onset and spinal onset (68.57 ± 14.20 vs. 79.30 ± 14.95 nM, respectively).Conclusion: HCSA is elevated in the blood of subjects with ALS. Since HCSA can be transported from the blood to the CNS by active transport, has neurotransmitter properties, and can activate synaptic receptors including NMDAR and metabotropic glutamate receptor, it is possible that increases in HCSA could influence glutamatergic neurotransmission and potentially contribute to excitotoxicity in some ALS patients.","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000517964","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39275602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Extending the Spectrum of Nonmotor Symptoms with Olfaction in Premotor Huntington's Disease: A Pilot Study. 扩大运动前亨廷顿病非运动症状与嗅觉的范围:一项初步研究

IF 3 4区医学

Neurodegenerative Diseases Pub Date : 2020-01-01 Epub Date: 2021-07-09 DOI: 10.1159/000518136

Beatrice Heim, Dora Valent, Federico Carbone, Sabine Spielberger, Florian Krismer, Atbin Djamshidian-Tehrani, Klaus Seppi

{"title":"Extending the Spectrum of Nonmotor Symptoms with Olfaction in Premotor Huntington's Disease: A Pilot Study.","authors":"Beatrice Heim, Dora Valent, Federico Carbone, Sabine Spielberger, Florian Krismer, Atbin Djamshidian-Tehrani, Klaus Seppi","doi":"10.1159/000518136","DOIUrl":"https://doi.org/10.1159/000518136","url":null,"abstract":"Objective: The aim of this pilot study was to investigate change of olfactory functions in Huntington's disease (HD).Background: HD is a neurodegenerative disease characterized by motor, cognitive, and behavioral abnormalities. There are several studies reporting olfactory dysfunction in manifest and some studies in premanifest HD carriers, and a recent neuropathological study demonstrated HD-specific protein aggregation in the anterior olfactory nucleus in HD patients. In this study, we wanted to assess olfactory functions as a possible early nonmotor symptom of HD mutation carriers without disease-specific motor symptoms and HD patients.Methods: All participants had genetic confirmed HD and were prospectively recruited during their routine control in a specialized outpatient clinic of the Medical University of Innsbruck, Department of Neurology, Austria. Healthy controls (HCs) were caregivers from patients. They were only included if they were younger than 70 years, scored more than 24/30 points on the Mini Mental State Examination, and had no other disease compromising olfactory function. Furthermore, all participants were tested on the Sniffin' sticks 16-items identification test.Results: We included 23 patients with manifest HD, 13 HD mutation carriers, and 19 HCs. Mutation carriers showed significant impaired odor identification compared to HCs (p < 0.001), as well as Huntington's patients compared with both mutation carriers (p = 0.003) and HCs (p < 0.001).Conclusions: The results of this pilot study suggest that olfactory dysfunction may be an early nonmotor symptom of HD and could be a potential marker to assess disease progression.","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000518136","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39275192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Alpha-Synuclein: The Interplay of Pathology, Neuroinflammation, and Environmental Factors in Parkinson's Disease. α -突触核蛋白:帕金森病病理、神经炎症和环境因素的相互作用。

IF 3 4区医学

Neurodegenerative Diseases Pub Date : 2020-01-01 Epub Date: 2021-01-19 DOI: 10.1159/000511083

Songzhe He, Shan Zhong, Gang Liu, Jun Yang

引用次数: 17

Cerebrospinal Fluid Alzheimer's Biomarkers and Neurofilament Light Profile of Idiopathic Normal Pressure Hydrocephalus in China: A PUMCH Cohort Study. 中国特发性常压脑积水的脑脊液阿尔茨海默病生物标志物和神经丝光谱:一项PUMCH队列研究

IF 3 4区医学

Neurodegenerative Diseases Pub Date : 2020-01-01 Epub Date: 2021-06-02 DOI: 10.1159/000514052

Chenhui Mao, Longze Sha, Caiyan Liu, Shanshan Chu, Jie Li, Xinying Huang, Dan Lei, Jie Wang, Liling Dong, Qi Xu, Bin Peng, Li-Ying Cui, Jing Gao

{"title":"Cerebrospinal Fluid Alzheimer's Biomarkers and Neurofilament Light Profile of Idiopathic Normal Pressure Hydrocephalus in China: A PUMCH Cohort Study.","authors":"Chenhui Mao, Longze Sha, Caiyan Liu, Shanshan Chu, Jie Li, Xinying Huang, Dan Lei, Jie Wang, Liling Dong, Qi Xu, Bin Peng, Li-Ying Cui, Jing Gao","doi":"10.1159/000514052","DOIUrl":"https://doi.org/10.1159/000514052","url":null,"abstract":"Introduction: Idiopathic normal pressure hydrocephalus (iNPH) is one of the potentially reversible dementias. Early and accurate diagnosis is important for patients' prognosis. Emerging evidence shows fluid biomarkers are useful in diagnosis and pathophysiological research of iNPH.Methods: Probable iNPH and Alzheimer's disease (AD) patients were recruited. Clinical diagnosis was performed according to international guidelines. CSF collection complied with a standard protocol. Commercial accessible ELISA kits were introduced for measurement of CSF t-tau, p-tau181, Aβ42, and NfL.Results: Twenty-seven iNPH, 27 AD, and 18 controls were included. The profiles of CSF t-tau, p-tau181, and t-tau/Aβ42 in the iNPH and AD were significantly different (p < 0.0001). The profiles of CSF t-tau, p-tau181, and t-tau/Aβ42 in the iNPH and control were not different (p > 0.05). Level of CSF Aβ42 in iNPH was significantly lower than control (p < 0.0001) and also significantly higher than AD (p < 0.05). NfL level in iNPH and AD was increased, but its level in iNPH was significantly lower than that in AD (p = 0.005). NfL and t-tau level in the iNPH group was significantly correlated (coefficient = 0.649, p = 0.005), but not in AD (coefficient = 0.298, p = 0.157).Conclusion: Alzheimer's CSF biomarker profile of iNPH subjects showed moderately decreased Aβ42 and normal t-tau, p-tau181, and t-tau/Aβ42, which was distinguishable from AD. The different profiles and correlation of t-tau and NfL suggested different pathophysiology of AD and iNPH. t-tau was relatively an AD-specific neurodegenerative biomarker compared to NfL.","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000514052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39054291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Ferroptosis Is Regulated by Mitochondria in Neurodegenerative Diseases. 神经退行性疾病中线粒体调控铁下垂

IF 3 4区医学

Neurodegenerative Diseases Pub Date : 2020-01-01 Epub Date: 2020-08-19 DOI: 10.1159/000510083

Juepu Zhou, Yao Jin, Yuhong Lei, Tianyi Liu, Zheng Wan, Hao Meng, Honglei Wang

{"title":"Ferroptosis Is Regulated by Mitochondria in Neurodegenerative Diseases.","authors":"Juepu Zhou, Yao Jin, Yuhong Lei, Tianyi Liu, Zheng Wan, Hao Meng, Honglei Wang","doi":"10.1159/000510083","DOIUrl":"https://doi.org/10.1159/000510083","url":null,"abstract":"Background: Neurodegenerative diseases are characterized by a gradual decline in motor and/or cognitive function caused by the selective degeneration and loss of neurons in the central nervous system, but their pathological mechanism is still unclear. Previous research has revealed that many forms of cell death, such as apoptosis and necrosis, occur in neurodegenerative diseases. Research in recent years has noticed that there is a new type of cell death in neurodegenerative diseases: ferroptosis. An increasing body of literature provides evidence for an involvement of ferroptosis in neurodegenerative diseases.Summary: In this article, we review a new form of cell death in neurodegenerative diseases: ferroptosis. Ferroptosis is defined as an iron-dependent form of regulated cell death, which occurs through the lethal accumulation of lipid-based reactive oxygen species when glutathione-dependent lipid peroxide repair systems are compromised. Several salient and established features of neurodegenerative diseases (including lipid peroxidation and iron dyshomeostasis) are consistent with ferroptosis, which means that ferroptosis may be involved in the progression of neurodegenerative diseases. In addition, as the center of energy metabolism in cells, mitochondria are also closely related to the regulation of iron homeostasis in the nervous system. At the same time, neurodegenerative diseases are often accompanied by degeneration of mitochondrial activity. Mitochondrial damage has been found to be involved in lipid peroxidation and iron dyshomeostasis in neurodegenerative diseases. Key Messages: Based on the summary of the related mechanisms of ferroptosis, we conclude that mitochondrial damage may affect neurodegenerative diseases by regulating many aspects of ferroptosis, including cell metabolism, iron dyshomeostasis, and lipid peroxidation.","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000510083","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38278668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 28

Assessment of the Corticospinal Tract Profile in Pure Lower Motor Neuron Disease: A Diffusion Tensor Imaging Study 单纯性下运动神经元疾病的皮质脊髓束轮廓评估：扩散张量成像研究

IF 3 4区医学

Neurodegenerative Diseases Pub Date : 2019-11-12 DOI: 10.1159/000503970

A. Sarica, P. Valentino, R. Nisticó, S. Barone, F. Pucci, A. Quattrone, A. Cerasa, A. Quattrone

{"title":"Assessment of the Corticospinal Tract Profile in Pure Lower Motor Neuron Disease: A Diffusion Tensor Imaging Study","authors":"A. Sarica, P. Valentino, R. Nisticó, S. Barone, F. Pucci, A. Quattrone, A. Cerasa, A. Quattrone","doi":"10.1159/000503970","DOIUrl":"https://doi.org/10.1159/000503970","url":null,"abstract":"Aim: The aim of this study was to evaluate the corticospinal tract (CST) diffusion profile in pure lower motor neuron disease (pLMND) patients who at baseline did not show any clinical or electrophysiological involvement of upper motor neurons (UMN), and in amyotrophic lateral sclerosis (ALS) patients. Materials and Methods: Fifteen ALS patients with delayed central motor conduction time (CMCT) and 14 pLMND patients with normal CMCT were enrolled together with 15 healthy controls. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) maps were obtained. The tract profile of CST was reconstructed with the automated fiber quantification tool and its diffusion properties were quantified voxel-by-voxel and then compared pairwise between groups. Moreover, a random forest (RF) classifier was trained to evaluate the ability of CST diffusion metrics in distinguishing pairwise the groups from the controls. Results: ALS patients presented wide microstructural abnormalities in the entire CST as assessed by FA decrease and RD increase while pLMND patients showed focal FA decrease and a larger AD increase in the cerebral peduncle and posterior limb of the internal capsule in comparison with controls. RF revealed that diffusion tensor imaging (DTI) metrics accurately distinguished ALS patients and pLMND patients from controls (96.67 and 95.71% accuracy, respectively). Conclusions: Our study demonstrates that the CST was impaired in both ALS and pLMND patients, thus suggesting that DTI metrics are a reliable tool in detecting subtle changes of UMN in pLMND patients, also in the absence of clinical and CMCT abnormalities.","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2019-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000503970","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49660526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Front & Back Matter 正面和背面

IF 3 4区医学

Neurodegenerative Diseases Pub Date : 2019-11-01 DOI: 10.1159/000505042

M. Hennerici, P. Unschuld, R. Nitsch

引用次数: 0

Is 123I-MIBG Scintigraphy Beneficial or Excessive for the Diagnosis of Parkinson’s Disease in the Early Phase? 123I-MIBG闪烁扫描术对早期帕金森病的诊断是有益的还是过度的？

IF 3 4区医学

Neurodegenerative Diseases Pub Date : 2019-11-01 DOI: 10.1159/000504006

T. Ikeda, S. Ikenoshita, Fumi Sakamoto, S. Shiraishi, K. Nakahara, T. Masuda, S. Yamashita

{"title":"Is 123I-MIBG Scintigraphy Beneficial or Excessive for the Diagnosis of Parkinson’s Disease in the Early Phase?","authors":"T. Ikeda, S. Ikenoshita, Fumi Sakamoto, S. Shiraishi, K. Nakahara, T. Masuda, S. Yamashita","doi":"10.1159/000504006","DOIUrl":"https://doi.org/10.1159/000504006","url":null,"abstract":"Introduction/Objective: In most cases, abnormal cardiac 123I-meta-iodobenzylguanidine (MIBG) scintigraphy increases the probability of a diagnosis of Parkinson’s disease (PD) in patients with parkinsonian features. In our study, we validated the additional value of 123I-MIBG scintigraphy beyond providing information on neurological findings and response to dopaminergic therapy for the diagnosis of PDin the early phase. Methods: We investigated 77 cases of PD (Hoehn and Yahr Stages I–III) and 73 cases of atypical parkinsonian disorder (APD), including 35 patients with multiple system atrophy, 19 with corticobasal syndrome, and 19 with progressive supranuclear palsy. Two multiple logistic regression models were developed to predict the probability of PD based on APD. Common covariates were resting tremor, vertical supranuclear palsy, apraxia, cerebellar symptoms, and response to dopaminergic therapy with MIBG scintigraphy (reference model) or without it (MIBG-added model). The net reclassification index (NRI) was examined and net benefit using decision curve analysis was performed to examine the additional clinical value of MIBG scintigraphy. Finally, we estimated the cost-effectiveness of MIBG scintigraphy. Results: The MIBG-added model significantly improved the ability to classify PD or APD compared with the reference model (NRI index 1.390, p < 0.001). However, the decision curve of the reference model ranked equally with the MIBG-added model up to a risk threshold of 0.8. In addition, MIBG scintigraphy was not cost-effective. Conclusions: Although MIBG scintigraphy has statistical usefulness for PD diagnosis, there may be little additional benefit in the early phase of PD beyond the neurological findings and response to dopaminergic therapy regarding clinical effectiveness and cost-effectiveness. It may be of greatest value when neurological findings that do not match PD are observed during the clinical course.","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000504006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42069507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Poor Diet, Stress, and Inactivity Converge to Form a “Perfect Storm” That Drives Alzheimer’s Disease Pathogenesis 不良饮食、压力和缺乏运动汇聚成一场“完美风暴”，驱动阿尔茨海默病的发病机制

IF 3 4区医学

Neurodegenerative Diseases Pub Date : 2019-10-10 DOI: 10.1159/000503451

Anthony G. Pacholko, C. A. Wotton, L. Bekar

{"title":"Poor Diet, Stress, and Inactivity Converge to Form a “Perfect Storm” That Drives Alzheimer’s Disease Pathogenesis","authors":"Anthony G. Pacholko, C. A. Wotton, L. Bekar","doi":"10.1159/000503451","DOIUrl":"https://doi.org/10.1159/000503451","url":null,"abstract":"North American incidence of Alzheimer’s disease (AD) is expected to more than double over the coming generation. Although genetic factors surrounding the production and clearance of amyloid-β and phosphorylated tau proteins are known to be responsible for a subset of early-onset AD cases, they do not explain the pathogenesis of the far more prevalent sporadic late-onset variant of the disease. It is thus likely that lifestyle and environmental factors contribute to neurodegenerative processes implicated in the pathogenesis of AD. Herein, we review evidence that (1) excess sucrose consumption induces AD-associated liver pathologies and brain insulin resistance, (2) chronic stress overdrives activity of locus coeruleus neurons, leading to loss of function (a common event in neurodegeneration), (3) high-sugar diets and stress promote the loss of neuroprotective sex hormones in men and women, and (4) Western dietary trends set the stage for a lithium-deficient state. We propose that these factors may intersect as part of a “perfect storm” to contribute to the widespread prevalence of neurodegeneration and AD. In addition, we put forth the argument that exercise and supplementation with trace lithium can counteract many of the deleterious consequences associated with excessive caloric intake and perpetual stress. We conclude that lifestyle and environmental factors likely contribute to AD pathogenesis and that simple lifestyle and dietary changes can help counteract their effects.","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2019-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000503451","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41321413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 18