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Brain activity in Parkinson's disease patients with mild cognitive impairment

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Science Bulletin 2016年第24期61卷 1876-1883页

作者： Linlin Gao Xuemin Wu Jiarong Zhang Piu Chan Tao Wu Department of Neurobiology Key Laboratory on Neurodegenerative Disorders of Ministry of Education Beijing Institute of Geriatrics Xuanwu Hospital Capital Medical University Beijing Key Laboratory on Parkinson’s Disease Parkinson Disease Center of Beijing Institute for Brain Disorders Community Health Station China University of Mining and Technology

Mild cognitive impairment(MCI) is common in patients with Parkinson's disease(PD), yet the underlying neural mechanisms of this disease state remain unclear. We investigated alterations in the spontaneous brain activity of PD patients with MCI(PD-MCI) relative to cognitively normal PD patients(PD-CN) and healthy control(HC)subjects. In this work, 13 PD-MCI patients, 16 PD-CN patients, and 16 HC subjects completed resting state functional MRI. Spontaneous brain activity was measured by calculating amplitude of low frequency fluctuation(ALFF) values across the whole brain. Between-group differences and correlations between ALFF values and cognitive test scores were analyzed. ALFF values decreased in the right superior temporal gyrus and increased in the left middle temporal gyrus and left superior frontal gyrus of PD-MCI patients compared with PD-CN patients. In the PD-MCI group, ALFF values in the left middle temporal gyrus were negatively correlated with Montreal Cognitive Assessment and vocabulary test scores,and the ALFF values in the left superior frontal gyrus were negatively correlated with vocabulary test scores. Our study demonstrates that PD-MCI is associated with abnormal spontaneous brain activity in the temporal and frontal lobes. These findings inform the underlying neural mechanism of cognitive impairment in PD.

关键词：帕金森病认知障碍脑活动患者功能磁共振成像认知功能障碍神经机制 ALF

Significance of the potential role of pharmacological MRI （phMRI） in diagnosis of Parkinson＇s disease

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Frontiers in Biology 2012年第4期7卷 307-312页

作者： Feng YUE Piu Chan Zhiming ZHANG Department of Neurobiology and Neurology Beijing Institute of Geriatrics Xuanwu Hospital of Capital University of Medical Sciences Beijing 100053 China Department of Anatomy and Neurobiology University of Kentucky College of Medicine Lexington KY 40536 USA

The initial diagnosis of Parkinson＇s disease （PD） is currently based on a clinical assessment. Many patients who receive an initial diagnosis of PD have parkinsonian features related to other diseases such as essential tremor, vascular parkinsonism and atypical parkinsonian disorder. It has been challenging to differentiate PD from those disorders, especially in the early disease stages, due to an overlap of clinical signs and symptoms. Therefore, there is a great need for development of noninvasive, highly sensitive, and widely available imaging methods that can potentially be used to assistant physicians to make more accurate diagnosis of the disease; and to longitudinally monitor treatment of PD. Recent advance of pharmacological MRI （phMRI） technology allows non-invasively mapping functional stages for nigrostriatal dopamine （DA） system. This article aims to review research findings primarily from our group in nonhuman primates modeling the neurodegenerative disease on the value of phMRI techniques in the diagnosis of PD.

关键词： pharmacological MRI （phMRI） Parkinson＇s disease phMRI techniques

Biomarker discovery for Parkinson’s disease

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Biomarker discovery for Parkinson’s disease

Anti-parkinsonian effects of octacosanol in 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-treated mice

中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Piu Chan Department of Neurology Neurobiology and GeriatricsBeijing Institute of GeriatricsXuanwu Hospital of Capital Medical University

＜正＞Parkinson’s disease（PD） is a chronic debilitating disease characterized by the selective and progressive loss of nigrostriatal dopamine neurons.The mechanisms underlying the pathophysiology of this disease are not fully understood.Mitochondrial dysfunction,oxidative damage,excitotoxicity,excessive iron accumulation and inflammation are likely to play a role in cell death.Currently it is believed that toxic environmental factors,along with a possible genetic susceptibility,may lead to disease development.One of the most imperative and challenging issues in PD field is to establish a standard for early diagnosis.On one hand,by the time patients with PD become symptomatic and seek medical treatment,60%-80%of the neurons in the substantia nigra pars compacta have been irreversibly lost,meaning the present clinical diagnostic means are not sensitive enough.On the other,although parkinson’s disease affects patients later in life,abundant evidence suggests the existence of a "preclinical" stage that could start years before a subject can be diagnosed clinically,when an individual appears normal but is developing extensive pathological changes in he brain.Therefore,early detection of PD is realizable,and in turn will improve disease management and enable potential neuroprotective therapies to be introduced at a stage when they would provide the greatest benefit.In addition,biomarkers would also be useful in monitoring the effectiveness of treatments for PD.To undertake the initiative for discovery of biomarkers for PD,efforts have been made to establish national consortium and community longitudinal cohorts using standardized protocols for collection of clinical information and tissue banks.In addition,non-human primate model for PD has also been established to mimic the pathological processes of PD for novel biomarker discovery.The talk will be focused on the establishment of the above-mentioned cohorts and models and preliminary results.

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来源： cnki会议评论

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Neural Regeneration Research 2012年第14期7卷 1080-1087页

作者： Tao Wang Yanyong Liu Nan Yang Chao Ji Piu Chan Pingping Zuo Department of Neurobiology Beijing Institute of Geriatrics Xuanwu Hospital of Capital Medical University Beijing 100053 China Department of Pharmacology Institute of Basic Medical Sciences Peking Union Medical College ＆ Chinese Academy of Medical Sciences Beijing 100005 China

Our previous research showed that octacosanol exerted its protective effects in 6-hydroxydopamine-induced Parkinsonian rats. The goal of this study was to investigate whether octacosanol would attenuate neurotoxicity in 1-methyl-4-phenyl-l,2,3,6 tetrahydropyridine （MPTP）-treated C57BL/6N mice and its potential mechanism. Behavioral tests, tyrosine hydroxylase immunohistochemistry and western blot were used to investigate the effects of octacosanol in a mouse model of Parkinson＇s disease. Oral administration of octacosanol （100 mg/kg） significantly improved behavioral impairments Jn mice treated by MPTP and markedly ameliorated morphological appearances of tyrosine hydroxylase-positive neuronal cells in the substantia nigra. Furthermore, octacosanol blocked MPTP-induced phosphorylation of p38MAPK and JNK, but not ERK1/2. These findings implicated that the protective effects afforded by octacosanol might be mediated by blocking the phosphorylation of p38MAPK and JNK on the signa transduction in vivo. Considering its excellent tolerability, octacosanol might be considered as a candidate agent for clinical application in treating Parkinson＇s disease.

关键词： Parkinson＇s disease neuroprotecion mitogen-activated protein kinase c-Jun N-terminal kinase p38MAPK substantia nigra neural regeneration

Early morning off in patients with Parkinson's disease:a Chinese nationwide study and a 7-question screening scale

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Translational Neurodegeneration 2020年第3期9卷 370-382页

作者： Chao Han Wei Mao Jing An Lifei Jiao Piu Chan on behalf of the China Early Morning Off(EMO)Study Group National Clinical Research Center for Geriatric Disorders Xuanwu Hospital of Capital Medical UniversityBeijingChina Department of Neurobiology Neurology and GeriatricsXuanwu Hospital of Capital Medical University45 Changchun RoadBeijing 100053China Beijing Institute of Geriatrics Xuanwu Hospital of Capital Medical University45 Changchun RoadBeijing 100053China Clinical Center for Parkinson's Disease Xuanwu Hospital of Capital Medical University45 Changchun RoadBejjing 100053China Key Laboratories for Neurodegenerative Diseases of the Ministry of Education Xuanwu Hospital of Capital Medical University45 Changchun RoadBeijing 100053China Bejjing Key Laboratory for Parkinson's Disease Xuanwu Hospital of Capital Medical University45 Changchun RoadBeijing 100053China Parkinson Disease Center of Beiing Institute for Brain Disorders Xuanwu Hospital of Capital Medical University45 Changchun RoadBeijing 100053China Advanced Innovative Center for Human Brain Protection Xuanwu Hospital of Capital Medical University45 Changchun RoadBejing 100053China Medical department Lundbeck(Bejjing)Pharmaceutical Co.ItdBeijingChina 不详

Background:Early morning off(EMO)is a common feature of Parkinson's disease(PD).This study aimed to characterize its clinical features and develop a convenient and pragmatic self-assessment instrument in a Chinese nationwide population.Methods:This study was conducted on 942 PD patients admitted to 55 clinic centers for movement disorders between June 2018 and May 2019 in China.Stepwise logistic regression analyses were performed to determine potential risk factors and the most predictive symptoms of EMO,as well as whether EMO was an independent risk factor of functional dependency in daily life.Based on this,a 7-question scale was derived for EMO screening.Diagnostic accuracy of this scale was assessed from the area under the receiver operative characteristic curve(AUROC)and its 95%confidence intervals(CIs).We further calculated sensitivity,specificity,positive predictive value(PPV),and negative predictive value(NPV)for the optimal cutoff point.Results:EMO occurred in 49.2%of PD patients across all disease stages.We identified 7 symptoms most predictive of EMO,including bradykinesia or rigidity,excessive sweating or salivation,ificulty in turning on or getting out of bed,muscle cramp,fatigue or sleepiness,frozen state or freezing gait,and tremor.The resulting 7-item scale was confirmed to be of good discrimination with a relatively large AUROC of 0.83,a relatively high sensitivity of 75.7%,specificity of 77.5%,PPV of 76.5%,and NPV of 76.7%.Nonideal nighttime sleep,long PD duration,advanced H&Y stages,posture instability gait difficulty-dominant or mixed subtypes,and high levodopa dose were independently associated with increased risk of EMO.EMO patients were at 87%higher(OR=1.87,95%C:1.07-3.32)risk of experiencing functional dependency in daily living compared with their counterparts.Conclusions:We demonstrated that EMO is a common feature for PD patients across all disease stages and put forward an EMO-specific screening card of sufficient accuracy and brevity.Meanwhile,we have thrown some light upon potential

关键词： Parkinson's disease Early morning off Motor symptoms Non-motor symptoms Screening scale

The underlying mechanism of prodromal PD:insights from the parasympathetic nervous system and the olfactory system

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Translational Neurodegeneration 2017年第1期6卷 20-28页

作者： Shu-Ying Liu Piu Chan A.Jon Stoessl Department of Neurobiology Neurology and GeriatricsXuanwu Hospital Capital Medical UniversityBeijing 100051China Beijing Key Laboratory on Parkinson’s Disease Parkinson Disease Center of Beijing Institute for Brain DisordersBeijing 100051China Pacific Parkinson’s Research Centre Division of Neurology and Djavad Mowafaghian Centre for Brain HealthUniversity of British Columbia and Vancouver Coastal HealthVancouver V6T 1Z3BCCanada

Neurodegeneration of Parkinson’s disease(PD)starts in an insidious manner,30–50%of dopaminergic neurons have been lost in the substantia nigra before clinical diagnosis.Prodromal stage of the disease,during which the disease pathology has started but is insufficient to result in clinical manifestations,offers a valuable window for disease-modifying therapies.The most focused underlying mechanisms linking the pathological pattern and clinical characteristics of prodromal PD are the prion hypothesis of alpha-synuclein and the selective vulnerability of neurons.In this review,we consider the two potential portals,the vagus nerve and the olfactory bulb,through which abnormal alpha-synuclein can access the brain.We review the clinical,pathological and neuroimaging evidence of the parasympathetic nervous system and the olfactory system in the neurodegenerative process and using the two systems as models to discuss the internal homogeneity and heterogeneity of the prodromal stage of PD,including both the clustering and subtyping of symptoms and signs.Finally,we offer some suggestions on future directions for imaging studies in prodromal Parkinson’s disease.

关键词： Parkinson’s disease Prodromal Alpha-synuclein Parasympathetic nervous system Olfactory system Subtype

Clinicogenetics of Parkinson’s disease:a drawing but not completed picture

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Neuroimmunology and Neuroinflammation 2014年第1期1卷 115-126页

作者： Chao-Dong Wang Piu Chan Department of Neurology The Affiliated Sanming First HospitalFujian Medical UniversitySanming 365000FujianChina Department of Neurobiology and Neurology Key Laboratory for Neurodegenerative Diseases of Ministry of EducationXuanwu Hospital of Capital Medical UniversityBeijing 100053China

Parkinson’s disease(PD)is a prevalent neurodegenerative disorder mainly affecting the population over the age of 60 years.The past decade has seen rapidly emerging data supporting a major importance of genetic factors in the development of PD.Increasing number of large-scale and replicating association studies has facilitated the confirmation of the possible predisposing factors to PD and the selection of genetic variants for risk prediction.While evidences are accumulating that variations within the SNCA,LRRK2,MAPT and GBA genes increase the individuals’vulnerability to PD,inconclusive or negative results have been reported for an association between PD and variants of the parkin,PINK1,DJ-1,UCH-L1,Omi/HtrA2,GIGYF2,PLA2G6,VPS35,EIF4G1 and BST1 genes.However,our understanding of the genetic picture of PD remains preliminary.Molecular diagnosis of the disease is only recommended for cases with clear family history,and currently,there is no ideal genomic biomarker available to predict the disease onset and progression,or to make a molecular classification of the disease.Efforts are expected to identify more genetic predisposing factors and to further clarify their roles in the mechanisms of PD.

关键词： Association biomarkers genetic variants Parkinson’s disease

Seropositivity rates of water channel protein 4 antibodies compared between a cell-based immunofluorescence assay and an enzyme-linked immunosorbent assay in neuromyelitis optica patients

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Neural Regeneration Research 2011年第32期6卷 2490-2494页

作者： Xiaoli Wu Zhangyuan Liao Jing Ye Huiqing Dong ChaodongWang Piu Chan Department of Neurology and Key Laboratory Ministry of Education on Neurodegenerative Diseases Xuanwu Hospital of Capital MedicalUniversity Beijing 100053 China Department of Neurology Xuanwu Hospital of Capital Medical University Beijing 100053 China

A total of 66 samples （from 27 cases with neuromyelitis optica, 26 cases with multiple sclerosis, aa 13 cases with optic neuritis） were tested for aquaporin-4 antibody by a cell-based immunofluorescence assay and an enzyme-linked immunosorbent assay. The sensitivities and specificities of the two assays were similar. We further analyzed an additional 68 patients and 93 healthy controls using the enzyme-linked immunosorbent assay. A Kappa test showed good consistency between the two methods in terms of detection of anti-aquaporin-4 antibody in the se of neuromyelitis optica patients. No significant correlations were identified with onset age or disea duration, suggesting that aquaporin-4 antibody is a good marker for neuromyelitis optica. The enzyme-linked immunosorbent assay can be used for quantifying aquaporin-4 antibody concentrations and may be useful to dynamically monitor changes in the levels of aquaporin-4 antibody during disease duration.

关键词： neuromyelitis optica cell-based immunofluorescence assay anti-aquaporin 4 antibody enzyme-linked immunosorbent assay long and extended spinal cord lesions neural regeneration

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帕金森病外周免疫机制研究进展

中华神经科杂志 2022年第10期55卷 1180-1184页

作者：刘疏影陈彪首都医科大学宣武医院神经内科国家老年疾病临床医学研究中心国家神经疾病医学中心北京100053

帕金森病是常见的老龄相关中枢神经系统神经退行性疾病,其发病机制为遗传易患因素、环境风险因素共同作用下的一系列病理生理变化。近年研究显示中枢神经系统以外的部位和机制,特别是免疫炎性反应等可能在帕金森病发病过程中起重要作用... 详细信息

帕金森病是常见的老龄相关中枢神经系统神经退行性疾病,其发病机制为遗传易患因素、环境风险因素共同作用下的一系列病理生理变化。近年研究显示中枢神经系统以外的部位和机制,特别是免疫炎性反应等可能在帕金森病发病过程中起重要作用。我们拟对目前已有的帕金森病外周免疫炎症机制研究结果进行综述,初步探讨其在帕金森病发病过程中的作用。

关键词：帕金森病炎症免疫发病机制