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Translational Neurodegeneration

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https://www.readbyqxmd.com/read/30410751/direct-conversion-of-mouse-astrocytes-into-neural-progenitor-cells-and-specific-lineages-of-neurons
#1
Kangmu Ma, Xiaobei Deng, Xiaohuan Xia, Zhaohuan Fan, Xinrui Qi, Yongxiang Wang, Yuju Li, Yizhao Ma, Qiang Chen, Hui Peng, Jianqing Ding, Chunhong Li, Yunlong Huang, Changhai Tian, Jialin C Zheng
Background: Cell replacement therapy has been envisioned as a promising treatment for neurodegenerative diseases. Due to the ethical concerns of ESCs-derived neural progenitor cells (NPCs) and tumorigenic potential of iPSCs, reprogramming of somatic cells directly into multipotent NPCs has emerged as a preferred approach for cell transplantation. Methods: Mouse astrocytes were reprogrammed into NPCs by the overexpression of transcription factors (TFs) Foxg1, Sox2, and Brn2...
2018: Translational Neurodegeneration
https://www.readbyqxmd.com/read/30410750/intranasal-rapamycin-ameliorates-alzheimer-like-cognitive-decline-in-a-mouse-model-of-down-syndrome
#2
Antonella Tramutola, Chiara Lanzillotta, Eugenio Barone, Andrea Arena, Ilaria Zuliani, Luciana Mosca, Carla Blarzino, D Allan Butterfield, Marzia Perluigi, Fabio Di Domenico
Background: Down syndrome (DS) individuals, by the age of 40s, are at increased risk to develop Alzheimer-like dementia, with deposition in brain of senile plaques and neurofibrillary tangles. Our laboratory recently demonstrated the disturbance of PI3K/AKT/mTOR axis in DS brain, prior and after the development of Alzheimer Disease (AD). The aberrant modulation of the mTOR signalling in DS and AD age-related cognitive decline affects crucial neuronal pathways, including insulin signaling and autophagy, involved in pathology onset and progression...
2018: Translational Neurodegeneration
https://www.readbyqxmd.com/read/30377523/aberrant-functional-connectivity-network-in-subjective-memory-complaint-individuals-relates-to-pathological-biomarkers
#3
Kaicheng Li, Xiao Luo, Qingze Zeng, Yeerfan Jiaerken, Xiaojun Xu, Peiyu Huang, Zhujing Shen, Jingjing Xu, Chao Wang, Jiong Zhou, Min-Ming Zhang
Background: Individuals with subjective memory complaints (SMC) feature a higher risk of cognitive decline and clinical progression of Alzheimer's disease (AD). However, the pathological mechanism underlying SMC remains unclear. We aimed to assess the intrinsic connectivity network and its relationship with AD-related pathologies in SMC individuals. Methods: We included 44 SMC individuals and 40 normal controls who underwent both resting-state functional MRI and positron emission tomography (PET)...
2018: Translational Neurodegeneration
https://www.readbyqxmd.com/read/30356861/alpha-synuclein-overexpression-in-the-olfactory-bulb-initiates-prodromal-symptoms-and-pathology-of-parkinson-s-disease
#4
Haichen Niu, Lingyu Shen, Tongzhou Li, Chao Ren, Sheng Ding, Lei Wang, Zhonghai Zhang, Xiaoyu Liu, Qiang Zhang, Deqin Geng, Xiujuan Wu, Haiying Li
Background: Parkinson's disease (PD) is a neurodegenerative disease characterized by intraneuronal Lewy Body (LB) aggregates composed of misfolded alpha-synuclein (α-syn). The spread of misfolded α-syn follows a typical pattern: starting in the olfactory bulb (OB) and the gut, this pathology is followed by the progressive invasion of misfolded α-syn to the posterior part of the brain. It is unknown whether the administration of human mutant alpha-synuclein (hm-α-syn, a human mutation which occurs in familial PD) into the OB of rats would trigger similar α-syn propagation and subsequently cause pathological changes in broader brain fields associated to PD and establish an animal model of prodromal PD...
2018: Translational Neurodegeneration
https://www.readbyqxmd.com/read/30338063/neurodegeneration-associated-fus-is-a-novel-regulator-of-circadian-gene-expression
#5
Xin Jiang, Tao Zhang, Haifang Wang, Tao Wang, Meiling Qin, Puhua Bao, Ruiqi Wang, Yuwei Liu, Hung-Chun Chang, Jun Yan, Jin Xu
Background: Circadian rhythms are oscillating physiological and behavioral changes governed by an internal molecular clock, and dysfunctions in circadian rhythms have been associated with ageing and various neurodegenerative diseases. However, the evidence directly connecting the neurodegeneration-associated proteins to circadian control at the molecular level remains sparse. Methods: Using meta-analysis, synchronized animals and cell lines, cells and tissues from FUS R521C knock-in rats, we examined the role of FUS in circadian gene expression regulation...
2018: Translational Neurodegeneration
https://www.readbyqxmd.com/read/30338062/csf-a%C3%AE-1-42-level-is-associated-with-cognitive-decline-in-early-parkinson-s-disease-with-rapid-eye-movement-sleep-behavior-disorder
#6
Maowen Ba, Guoping Yu, Min Kong, Hui Liang, Ling Yu
Background: Rapid eye movement sleep behavior disorder (RBD) is associated with cognitive decline in early Parkinson's disease (PD). However, the underlyling basis for this association remains unclear. Methods: Parkinson's Progression Marker's Initiative (PPMI) subjects underwent baseline RBD testing with RBD sleep questionnaire (RBDSQ). Serial assessments included measures of motor symptoms, non-motor symptoms (NMS), neuropsychological assessment, blood and cerebrospinal fluid (CSF) biomarkers...
2018: Translational Neurodegeneration
https://www.readbyqxmd.com/read/30311914/cerebrospinal-fluid-phosphorylated-tau-visinin-like-protein-1-and-chitinase-3-like-protein-1-in-mild-cognitive-impairment-and-alzheimer-s-disease
#7
Hua Zhang, Kok Pin Ng, Joseph Therriault, Min Su Kang, Tharick A Pascoal, Pedro Rosa-Neto, Serge Gauthier
Background: Visinin-like protein-1 (VILIP-1) and chitinase-3-like protein 1 (CHI3L1 or YKL-40) in cerebrospinal fluid (CSF) are newly discovered markers indicating neuronal damage and microglial activation, respectively. Phosphorylated tau (p-tau) reflects the neuropathology of Alzheimer's disease (AD) and is useful as diagnostic markers for AD. However, it is unknown whether these biomarkers have similar or complementary information in AD. Methods: We stratified 121 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database into cognitively normal (CN), stable mild cognitive impairment (sMCI), progressive MCI (pMCI), and dementia due to AD...
2018: Translational Neurodegeneration
https://www.readbyqxmd.com/read/30237878/bis-9-meptazinol-a-novel-dual-binding-ache-inhibitor-rescues-cognitive-deficits-and-pathological-changes-in-app-ps1-transgenic-mice
#8
Yuhuan Shi, Wanying Huang, Yu Wang, Rui Zhang, Lina Hou, Jianrong Xu, Zhuibai Qiu, Qiong Xie, Hongzhuan Chen, Yongfang Zhang, Hao Wang
Background: Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative brain disorder, which is the most common form of dementia. Intensive efforts have been made to find effective and safe treatment against AD. Acetylcholinesterase inhibitors (AChEIs) have been widely used for the treatment of mild to moderate AD. In this study, we investigated the effect of Bis(9)-(-)-Meptazinol (B9M), a novel potential dual-binding acetylcholinesterase (AChE) inhibitor, on learning and memory abilities, as well as the underlying mechanism in the APP/PS1 mouse model of AD...
2018: Translational Neurodegeneration
https://www.readbyqxmd.com/read/30147869/objective-assessment-of-bradykinesia-in-parkinson-s-disease-using-evolutionary-algorithms-clinical-validation
#9
Chao Gao, Stephen Smith, Michael Lones, Stuart Jamieson, Jane Alty, Jeremy Cosgrove, Pingchen Zhang, Jin Liu, Yimeng Chen, Juanjuan Du, Shishuang Cui, Haiyan Zhou, Shengdi Chen
Background: There is an urgent need for developing objective, effective and convenient measurements to help clinicians accurately identify bradykinesia. The purpose of this study is to evaluate the accuracy of an objective approach assessing bradykinesia in finger tapping (FT) that uses evolutionary algorithms (EAs) and explore whether it can be used to identify early stage Parkinson's disease (PD). Methods: One hundred and seven PD, 41 essential tremor (ET) patients and 49 normal controls (NC) were recruited...
2018: Translational Neurodegeneration
https://www.readbyqxmd.com/read/30128146/ultra-high-field-diffusion-mri-reveals-early-axonal-pathology-in-spinal-cord-of-als-mice
#10
Rodolfo G Gatto, Manish Y Amin, Daniel Deyoung, Matthew Hey, Thomas H Mareci, Richard L Magin
Background: Amyotrophic lateral sclerosis (ALS) is a disease characterized by a progressive degeneration of motor neurons leading to paralysis. Our previous MRI diffusion tensor imaging studies detected early white matter changes in the spinal cords of mice carrying the G93A-SOD1 mutation. Here, we extend those studies using ultra-high field MRI (17.6 T) and fluorescent microscopy to investigate the appearance of early structural and connectivity changes in the spinal cords of ALS mice...
2018: Translational Neurodegeneration
https://www.readbyqxmd.com/read/30128145/dopaminergic-neurons-show-increased-low-molecular-mass-protein-7-activity-induced-by-6-hydroxydopamine-in-vitro-and-in-vivo
#11
Ming-Shu Mo, Gui-Hua Li, Cong-Cong Sun, Shu-Xuan Huang, Lei Wei, Li-Min Zhang, Miao-Miao Zhou, Zhuo-Hua Wu, Wen-Yuan Guo, Xin-Ling Yang, Chao-Jun Chen, Shao-Gang Qu, Jian-Xing He, Ping-Yi Xu
Background: Abnormal expression of major histocompatibility complex class I (MHC-I) is increased in dopaminergic (DA) neurons in the substantia nigra (SN) in Parkinson's disease (PD). Low-molecular-mass protein 7 (β5i) is a proteolytic subunit of the immunoproteasome that regulates protein degradation and the MHC pathway in immune cells. Methods: In this study, we investigated the role of β5i in DA neurons using a 6-hydroxydopamine (6-OHDA) model in vitro and vivo ...
2018: Translational Neurodegeneration
https://www.readbyqxmd.com/read/30065816/properties-of-oscillatory-neuronal-activity-in-the-basal-ganglia-and-thalamus-in-patients-with-parkinson-s-disease
#12
G Du, P Zhuang, M Hallett, Y-Q Zhang, J-Y Li, Y-J Li
Background: The cardinal features of Parkinson's disease (PD) are bradykinesia, rigidity and rest tremor. Abnormal activity in the basal ganglia is predicted to underlie the mechanism of motor symptoms. This study aims to characterize properties of oscillatory activity in the basal ganglia and motor thalamus in patients with PD. Methods: Twenty-nine patients with PD who underwent bilateral or unilateral electrode implantation for subthalamic nucleus (STN) DBS ( n  = 11), unilateral pallidotomy ( n  = 9) and unilateral thalamotomy (n = 9) were studied...
2018: Translational Neurodegeneration
https://www.readbyqxmd.com/read/30062008/the-role-of-substantia-nigra-sonography-in-the-differentiation-of-parkinson-s-disease-and-multiple-system-atrophy
#13
Hai-Yan Zhou, Pei Huang, Qian Sun, Juan-Juan Du, Shi-Shuang Cui, Yun-Yun Hu, Wei-Wei Zhan, Ying Wang, Qin Xiao, Jun Liu, Yu-Yan Tan, Sheng-Di Chen
Background: The differential diagnosis of Parkinson's disease (PD) and multiple system atrophy (MSA) remains a challenge, especially in the early stage. Here, we assessed the value of transcranial sonography (TCS) to discriminate non-tremor dominant (non-TD) PD from MSA with predominant parkinsonism (MSA-P). Methods: Eighty-six MSA-P patients and 147 age and gender-matched non-TD PD patients who had appropriate temporal acoustic bone windows were included in this study...
2018: Translational Neurodegeneration
https://www.readbyqxmd.com/read/30038782/cognitive-characteristics-in-chinese-non-demented-pd-patients-based-on-gender-difference
#14
Ke Yang, Bo Shen, Da-Ke Li, Ying Wang, Jue Zhao, Jian Zhao, Wen-Bo Yu, Zhen-Yang Liu, Yi-Lin Tang, Feng-Tao Liu, Huan Yu, Jian Wang, Qi-Hao Guo, Jian-Jun Wu
Background: Cognitive impairment is one of the non-motor symptoms in Parkinson's disease (PD). In the present study, we aim to examine the cognitive function of non-demented Parkinson's disease patients and compare the results between male and female patients as well as control groups in search of any gender effect. Methods: Sixty PD Patients (30 males and 30 females) from the Movement Disorders Clinic at Huashan Hospital Affiliated to Fudan University were recruited to participate in the study...
2018: Translational Neurodegeneration
https://www.readbyqxmd.com/read/29988514/adjunct-rasagiline-to-treat-parkinson-s-disease-with-motor-fluctuations-a-randomized-double-blind-study-in-china
#15
Zhenxin Zhang, Ming Shao, Shengdi Chen, Chunfeng Liu, Rong Peng, Yansheng Li, Jian Wang, Suiqiang Zhu, Qiumin Qu, Xiaoying Zhang, Haibo Chen, Xiangru Sun, Yanping Wang, Shenggang Sun, Baorong Zhang, Jimei Li, Xiaoping Pan, Gang Zhao
Background: The use of adjunct rasagiline in levodopa-treated patients with Parkinson's disease and motor fluctuations is supported by findings from large-scale clinical studies. This study is to investigate the efficacy and safety of adjunct rasagiline in Chinese patients with Parkinson's disease, as a product registration study. Methods: This 16-week, randomized, double-blind, parallel-group, multicenter, placebo-controlled study of rasagiline 1 mg/day included levodopa-treated patients with Parkinson's disease and motor fluctuations...
2018: Translational Neurodegeneration
https://www.readbyqxmd.com/read/29988485/age-dependent-alpha-synuclein-accumulation-and-aggregation-in-the-colon-of-a-transgenic-mouse-model-of-parkinson-s-disease
#16
Qian-Qian Chen, Caroline Haikal, Wen Li, Ming-Tao Li, Zhan-You Wang, Jia-Yi Li
Background: Parkinson's disease (PD) is one of the most common neurodegenerative diseases, neuropathologically characterized by misfolded protein aggregation, called Lewy bodies and Lewy neurites. PD is a slow-progressive disease with colonic dysfunction appearing in the prodromal stage and lasting throughout the course of the disease. Methods: In order to study PD pathology in the colon, we examined the age-dependent morphological and pathological changes in the colon of a PD mouse model expressing human wildtype α-synuclein (α-syn) fused with the green fluorescent protein (GFP), under the endogenous mouse α-syn promoter...
2018: Translational Neurodegeneration
https://www.readbyqxmd.com/read/29876101/impact-of-the-biological-definition-of-alzheimer-s-disease-using-amyloid-tau-and-neurodegeneration-atn-what-about-the-role-of-vascular-changes-inflammation-lewy-body-pathology
#17
REVIEW
S Gauthier, H Zhang, K P Ng, T A Pascoal, P Rosa-Neto
Background: The NIA-AA research framework proposes a biological definition of Alzheimer's disease, where asymptomatic persons with amyloid deposition would be considered as having this disease prior to symptoms. Discussion: Notwithstanding the fact that amyloid deposition in isolation is not associated with dementia, even the combined association of amyloid and tau pathology does not inevitably need to dementia over age 65. Other pathological factors may play a leading or an accelerating role in age-associated cognitive decline, including vascular small vessel disease, neuroinflammation and Lewy Body pathology...
2018: Translational Neurodegeneration
https://www.readbyqxmd.com/read/29719720/chinese-expert-consensus-on-programming-deep-brain-stimulation-for-patients-with-parkinson-s-disease
#18
REVIEW
Shengdi Chen, Guodong Gao, Tao Feng, Jianguo Zhang
Background: Deep Brain Stimulation (DBS) therapy for the treatment of Parkinson's Disease (PD) is now a well-established option for some patients. Postoperative standardized programming processes can improve the level of postoperative management and programming, relieve symptoms and improve quality of life. Main body: In order to improve the quality of the programming, the experts on DBS and PD in neurology and neurosurgery in China reviewed the relevant literatures and combined their own experiences and developed this expert consensus on the programming of deep brain stimulation in patients with PD in China...
2018: Translational Neurodegeneration
https://www.readbyqxmd.com/read/29719719/divergent-topological-networks-in-alzheimer-s-disease-a-diffusion-kurtosis-imaging-analysis
#19
Jia-Xing Cheng, Hong-Ying Zhang, Zheng-Kun Peng, Yao Xu, Hui Tang, Jing-Tao Wu, Jun Xu
Background: Brain consists of plenty of complicated cytoarchitecture. Gaussian-model based diffusion tensor imaging (DTI) is far from satisfactory interpretation of the structural complexity. Diffusion kurtosis imaging (DKI) is a tool to determine brain non-Gaussian diffusion properties. We investigated the network properties of DKI parameters in the whole brain using graph theory and further detected the alterations of the DKI networks in Alzheimer's disease (AD). Methods: Magnetic resonance DKI scanning was performed on 21 AD patients and 19 controls...
2018: Translational Neurodegeneration
https://www.readbyqxmd.com/read/29713467/cerebral-glucose-metabolic-prediction-from-amnestic-mild-cognitive-impairment-to-alzheimer-s-dementia-a-meta-analysis
#20
REVIEW
Hai Rong Ma, Li Qin Sheng, Ping Lei Pan, Gen Di Wang, Rong Luo, Hai Cun Shi, Zhen Yu Dai, Jian Guo Zhong
Brain 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) has been utilized to monitor disease conversion from amnestic mild cognitive impairment (aMCI) to Alzheimer's dementia (AD). However, the conversion patterns of FDG-PET metabolism across studies are not conclusive. We conducted a voxel-wise meta-analysis using Seed-based d Mapping that included 10 baseline voxel-wise FDG-PET comparisons between 93 aMCI converters and 129 aMCI non-converters from nine longitudinal studies. The most robust and reliable metabolic alterations that predicted conversion from aMCI to AD were localized in the left posterior cingulate cortex (PCC)/precuneus...
2018: Translational Neurodegeneration
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