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Consensus on rapid screening for prodromal Alzheimer's disease in China

General Psychiatry 2024年第1期37卷 1-16页

作者： Lin Huang Qinjie Li Yao Lu Fengfeng Pan Liang Cui Ying Wang Ya Miao Tianlu Chen Yatian Li Jingnan Wu Xiaochun Chen jianping jia Qihao Guo Department of Gerontology Shanghai Sixth People's Hospital Afiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina shanghai BestCovered ShanghaiChina ADepartment of Neurology Fujan Medical University Union HospitalFuzhouChina Department of Neurology National Clinical Research Center for Geriatric DiseasesBeijingChina

Alzheimer's disease(AD)is a common cause of dementia,characterised by cerebral amyloid-βdeposition,pathological tau and neurodegeneration.The prodromal stage of AD(pAD)refers to patients with mild cognitive impairment(MCl)and evidence of AD's pathology.At this stage,disease-modifying interventions should be used to prevent the progression to dementia.Given the inherent heterogeneity of MCl,more specific biomarkers are needed to elucidate the underlying AD's pathology.Although the uses of cerebrospinal fluid and positron emission tomography are widely accepted methods for detecting AD's pathology,their clinical applications are limited by their high costs and invasiveness,particularly in low-income areas in China.Therefore,to improve the early detection of Alzheimer's disease(AD)pathology through cost-effective screening methods,a panel of 45neurologists,psychiatrists andgerontologistswas invited to establish a formal consensus on the screening of pAD in China.The supportive evidence and grades of recommendations are based on a systematic literature review andfocus group discussion.National meetings were held to allow participants to review,vote and provide their expert opinions to reach a consensus.A majority(two-thirds)decision was used for questions for which consensus could not be reached.Recommended screening methods are presented in this publication,including neuropsychological assessment,peripheral biomarkers and brain imaging.In addition,a general workflow for Screening pAD in China is established,which will help clinicians identify individuals at high risk and determine therapeutic targets.

关键词： Alzheimer income screening

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Critical thinking of Alzheimer's transgenic mouse model:current research and future perspective

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Science China(Life Sciences) 2023年第12期66卷 2711-2754页

作者： Xinyue Li Meina Quan Yiping Wei Wei Wang Lingzhi Xu Qi Wang jianping jia Innovation Center for Neurological Disorders and Department of Neurology Xuanwu HospitalCapital Medical UniversityBeijing 100053China National Medical Center for Neurological Diseases and National Clinical Research Center for Geriatric Diseases Beijing 100053China Beijing Key Laboratory of Geriatric Cognitive Disorders Beijing 100053China Clinical Center for Neurodegenerative Disease and Memory Impairment Capital Medical UniversityBeijing 100053China Center of Alzheimer’s Disease Beijing Institute of Brain DisordersCollaborative Innovation Center for Brain DisordersCapital Medical UniversityBeijing 100053China Key Laboratory of Neurodegenerative Diseases Ministry of EducationBeijing 100053China

Transgenic models are useful tools for studying the pathogenesis of and drug development for Alzheimer's Disease(AD).AD models are constructed usually using overexpression or knock-in of multiple pathogenic gene mutations from familial AD.Each transgenic model has its unique behavioral and pathological features.This review summarizes the research progress of transgenic mouse models,and their progress in the unique mechanism of amyloid-βoligomers,including the first transgenic mouse model built in China based on a single gene mutation(PSEN1 V97L)found in Chinese familial AD.We further summarized the preclinical findings of drugs using the models,and their future application in exploring the upstream mechanisms and multi-target drug development in AD.

关键词： Alzheimer's disease transgenic mouse model amyloid-βoligomers multi-target therapy

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Genetic Phenotypes of Alzheimer’s Disease:Mechanisms and Potential Therapy

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Phenomics 2023年第4期3卷 333-349页

作者： Meina Quan Shuman Cao Qi Wang Shiyuan Wang jianping jia Innovation Center for Neurological Disorders and Department of Neurology Xuanwu HospitalCapital Medical UniversityBeijing 100053China National Medical Center for Neurological Disorders and National Clinical Research Center for Geriatric Diseases Beijing 100053China Beijing Key Laboratory of Geriatric Cognitive Disorders Beijing 100053China Clinical Center for Neurodegenerative Disease and Memory Impairment Capital Medical UniversityBeijing 100053China Center of Alzheimer’s Disease Collaborative Innovation Center for Brain DisordersBeijing Institute of Brain DisordersCapital Medical UniversityBeijing 100053China Key Laboratory of Neurodegenerative Diseases Ministry of EducationBeijing 100053China

Years of intensive research has brought us extensive knowledge on the genetic and molecular factors involved in Alzheimer's disease(AD).In addition to the mutations in the three main causative genes of familial AD(FAD)including presenilins and amyloid precursor protein genes,studies have identified several genes as the most plausible genes for the onset and progression of FAD,such as triggering receptor expressed on myeloid cells 2,sortilin-related receptor 1,and adenosine triphosphate-binding cassette transporter subfamily A member 7.The apolipoprotein Eε4 allele is reported to be the strongest genetic risk factor for sporadic AD(SAD),and it also plays an important role in FAD.Here,we reviewed recent developments in genetic and molecular studies that contributed to the understanding of the genetic phenotypes of FAD and compared them with SAD.We further reviewed the advancements in AD gene therapy and discussed the future perspectives based on the genetic phenotypes.

关键词： Alzheimer's disease Genetic phenotypes Molecular mechanism Gene therapy

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Vulnerability assessment of coastal wetlands in Minjiang River Estuary based on cloud model under sea level rise

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Acta Oceanologica Sinica 2023年第7期42卷 160-174页

作者： Xiaohe Lai Chuqing Zeng Yan Su Shaoxiang Huang jianping jia Cheng Chen Jun jiang Department of Water Resources and Harbor Engineering College of Civil EngineeringFuzhou UniversityFuzhou 350108China Fujian Institute of Geological Survey Fuzhou 350108China

The change of coastal wetland vulnerability affects the ecological environment and the economic development of the estuary area.In the past,most of the assessment studies on the vulnerability of coastal ecosystems stayed in static qualitative research,lacking predictability,and the qualitative and quantitative relationship was not objective enough.In this study,the“Source-Pathway-Receptor-Consequence”model and the Intergovernmental Panel on Climate Change vulnerability definition were used to analyze the main impact of sea level rise caused by climate change on coastal wetland ecosystem in Minjiang River Estuary.The results show that:(1)With the increase of time and carbon emission,the area of high vulnerability and the higher vulnerability increased continuously,and the area of low vulnerability and the lower vulnerability decreased.(2)The eastern and northeastern part of the Culu Island in the Minjiang River Estuary of Fujian Province and the eastern coastal wetland of Meihua Town in Changle District are areas with high vulnerability risk.The area of high vulnerability area of coastal wetland under high emission scenario is wider than that under low emission scenario.(3)Under different sea level rise scenarios,elevation has the greatest impact on the vulnerability of coastal wetlands,and slope has less impact.The impact of sea level rise caused by climate change on the coastal wetland ecosystem in the Minjiang River Estuary is mainly manifested in the sea level rise,which changes the habitat elevation and daily flooding time of coastal wetlands,and then affects the survival and distribution of coastal wetland ecosystems.

关键词： vulnerability assessment cloud model coastal wetland Minjiang River Estuary

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An Overview of Genome-Wide Association Studies in Alzheimer＇s Disease

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Neuroscience Bulletin 2016年第2期32卷 183-190页

作者： Luxi Shen jianping jia Department of Neurology Xuan Wu Hospital of the Capital Medical University Beijing 100053 China Center of Alzheimer's Disease Beijing Institute for Brain Disorders Beijing 100053 China Beijing Key Laboratory of Geriatric Cognitive Disorders Beijing 100053 China Neurodegenerative Laboratory of Ministry of Education of the People's Republic of China Beijing 100053 China

Genome-wide association studies（GWASs）have revealed a plethora of putative susceptibility genes for Alzheimer＇s disease（AD）. With the sole exception of the APOE gene, these AD susceptibility genes have not been unequivocally validated in independent studies. No single novel functional risk genetic variant has been identified. In this review, we evaluate recent GWASs of AD, and discuss their significance, limitations, and challenges in the investigation of the genetic spectrum of AD.

关键词： Association analysis Alzheimer’s disease susceptibility genes Apolipoprotein E Common variant

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Genetic association of urokinase-type plasminogen activator gene rs2227564 site polymorphism with sporadic Alzheimer's disease in the Han Chinese population

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Neural Regeneration Research 2012年第30期7卷 2377-2383页

作者： Xuelian Ji Longfei jia jianping jia Li Qi Department of Neurology Inner Mongolia People's Hospital Huhhot 010017 Inner Mongolia Autonomous Region China Department of Neurology Xuanwu Hospital Capital Medical University Beijing 100053 China Inner Mongolia Corps Hospital Chinese People's Armed Police Forces Huhhot 010040 Inner Mongolia Autonomous Region China

A missense C/T polymorphism in exon 6 （the NCBI rslD is rs2227564） of the urokinase-type plasminogen activator gene has been identified as a possible hot spot for Alzheimer＇s disease risk. The present study analyzed urokinase-type plasminogen gene polymorphisms of rs2227564 with sporadic Alzheimer＇s disease by PCR-restriction fragment length polymorphism. Results showed that CC, CT and TT genotype distribution frequencies had significant differences between sporadic Aizheimer＇s disease patients and healthy controls, in-depth analysis of the association between urokinase-type plasminogen gene rs2227564 polymorphisms and sporadic Alzheimer＇s disease indicated that people with the C-positive genotype CC ＋ CT were at a higher risk for developing sporadic Alzheimer＇s disease. These results support the contribution of the polymorphisms of rs2227564 in the urokinase-type plasminogen gene to the pathogenesis of sporadicAIzheimer＇s disease in the Han Chinese population.

关键词： Alzheimer＇s disease urokinase plasminogen activator polymorphism genetic testing Han Chinesepopulation neural regeneration

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Advances in longitudinal studies of amnestic mild cognitive impairment and Alzheimer's disease based on multi-modal MRI techniques

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Neuroscience Bulletin 2014年第2期30卷 198-206页

作者： Zhongjie Hu Liyong Wu jianping jia Ying Han Department of Neurology Xuan Wu Hospital Capital Medical University Postgraduates Institute Capital Medical University Alzheimer's Disease Center Beijing Institute for Brain Disorders

Amnestic mild cognitive impairment （aMCI） is a prodromal stage of Alzheimer＇s disease （AD）, and 75%-80% of aMCI patients finally develop AD. So, early identification of patients with aMCI or AD is of great significance for prevention and intervention. According to cross-sectional studies, it is known that the hippocampus, posterior cingulate cortex, and corpus callosum are key areas in studies based on structural MRI （sMRI）, functional MRI （fMRI）, and diffusion tensor imaging （DTI） respectively. Recently, longitudinal studies using each MRI modality have demonstrated that the neuroimaging abnormalities generally involve the posterior brain regions at the very beginning and then gradually affect the anterior areas during the progression of aMCI to AD. However, it is not known whether follow-up studies based on multi-modal neuroimaging techniques （e.g., sMRI, fMRI, and DTI） can help build effective MRI models that can be directly applied to the screening and diagnosis of aMCI and AD. Thus, in the future, large-scale multi-center follow-up studies are urgently needed, not only to build an MRI diagnostic model that can be used on a single person, but also to evaluate the variability and stability of the model in the general population. In this review, we present longitudinal studies using each MRI modality separately, and then discuss the future directions in this field.

关键词： magnetic resonance imaging amnestic mild cognitive impairment Alzheimer＇s disease multi-modality longitudinal studies

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Dementia studies in Chinese populations

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Neuroscience Bulletin 2014年第2期30卷 207-216页

作者： Jin-Jing Pei Maria Stella T. Giron jianping jia Hui-Xin Wang Department of Neurology Xuan Wu Hospital Capital Medical University Beijing 100053 China KI-Alzheimer's Disease Research Center Department of Neurobiology Care Sciences and Society Karolinska InstitutetNovum 141 86 Stockholm Sweden Aging Research Center Department of Neurobiology Care Sciences and Society Karolinska Institutet and StockholmUniversity G~vlegatan 16 113 30 Stockholm Sweden

Variations in the prevalence of dementia in different ethnic groups have been reported worldwide, and a number of reviews have provided a picture of epidemiological studies in dementia research. However, little is known about epidemiological studies in Chinese populations. In this review, we searched PubMed and the Web of Science for original research articles published in English up to July 2013 on the prevalence, incidence, risk factors, and prognosis of dementia in Chinese populations worldwide. Except for the prevalence, we included only population-based follow-up studies. We identified 25 studies in elderly Chinese residents in China's Mainland, Hong Kong, Taiwan, and Singapore, and found a higher prevalence of dementia in China's Mainland than in the other locations, which may be due to that the studies from China's Mainland are more recent than those from other locations. A notable increase in incidence was observed when dementia cases were diagnosed using 10/66 diagnostic criteria compared to other criteria. Studies on risk factors for dementia were limited and mostly from China's Mainland. Age, gender, education, smoking, and alcohol consumption were related to the risk of dementia in Chinese populations. Only two prognostic studies were identified, and age, gender, and residential area were related to the prognosis of dementia. In conclusion, the prevalence, incidence, and risk factors for dementia found in Chinese populations were comparable to other ethnic groups, but no conclusive results on prognosis were found. The differences in prevalence and incidence were influenced by the diagnostic criteria and the time of study. Longitudinal population-based studies on the incidence, risk factors, and prognosis of dementia in Chinese populations are required.

关键词： dementia epidemiology risk factors prognosis prevalence incidence

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冷金属过渡电弧增材制造5183铝合金温度场的数值模拟

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机械工程材料 2024年第1期48卷 106-111页

作者：贾剑平李田雨南昌大学先进制造学院南昌330031

利用有限元分析软件ABAQUS使用生死单元法建立冷金属过渡(CMT)电弧增材制造单道10层5183铝合金模型,模拟分析了增材制造过程中温度场的分布和变化规律,并进行试验验证;采用该模拟方法研究了增材制造路径(单向和交叉路径)、层间冷却时间(... 详细信息

利用有限元分析软件ABAQUS使用生死单元法建立冷金属过渡(CMT)电弧增材制造单道10层5183铝合金模型,模拟分析了增材制造过程中温度场的分布和变化规律,并进行试验验证;采用该模拟方法研究了增材制造路径(单向和交叉路径)、层间冷却时间(20,40,60 s)和焊接速度(400,450,500 mm·min^(-1))对温度场的影响。结果表明:模拟得到在CMT电弧增材制造过程中基板某点的热循环曲线的变化趋势与试验结果基本一致,且峰值温度和波谷温度与试验结果的相对误差均不大于8.93%,验证了模型的准确性。随着堆焊层数的增加,熔池峰值温度升高,熔池区域变大;单向路径增材制造会在试样收弧端产生较严重的热积累,而交叉路径可以减弱热积累效应;层间冷却时间越长,焊道中点的峰值温度越低,且降低幅度随冷却时间的延长而逐渐减弱;焊道的峰值温度和波谷温度随焊接速度的增加而降低。

关键词：电弧增材制造冷金属过渡数值模拟温度场

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Northern Chinese Han populations with sporadic Alzheimer’s disease and the role of urokinase-type plasminogen activator gene promoter polymorphisms

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Neural Regeneration Research 2010年第2期5卷 150-155页

作者： Di Han Yan Wang Hongyun Li jianping jia Department of Emergency Neurology Medical School Hospital of Qingdao University Qingdao 266003 Shandong Province China Department of Neurology Medical School Hospital of Qingdao University Qingdao 266003 Shandong Province China Department of Neurology Xuanwu Hospital of the Capital Medical University Beijing 100053 China

BACKGROUND; Polymorphisms of urokinase-type plasminogen activator gene （PLAU） have recently been reported to be associated with sporadic Alzheimer＇ disease （SAD）. However, most studies have focused on the exon region of this gene, and there is no report on the association between promoter polymorphisms of the PLAU and SAD. OBJECTIVE： To determine whether SAD is associated with promoter polymorphisms of PLAU in Northem Han Chinese. DESIGN, TIME AND SETTING： A case-control study was performed at Neurology Laboratory of Xuanwu Hospital of the Capital Medical University from September 2006 to July 2008. PARTICIPANTS： A total of 397 participants living in Beijing were assigned to SAD [n = 196, including 103 males and 93 females, mean age of （64 ± 7） years] and control [n = 201, including 108 males and 93 females, mean age of （68 ± 6） years] groups. The patients were diagnosed and met the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer＇s Disease and Related Disorder Association criteria for possible Alzheimer＇s disease. Controls received clinical, mental, and neurological examinations to rule out cognitive deficiencies. All controls had Mini-Mental Status Examination scores 〉 27. METHODS： Genotypes of PLAU and apolipoprotein-E were examined in 196 patients with SAD and 201 age- and sex-matched controls from the same community using polymerase chain reaction-restriction fragment length polymorphism method. SPSS 11.5 software was used for data analysis, distribution of allele and genotypic frequency were calculated, and Hardy-Weinberg was also performed in this study. MAIN OUTCOME MEASURES： The main outcome measures were allele and genotype frequency differences in the promoter region of the PLAU gene between SAD and control subjects. RESULTS： In Chinese Han populations, the two polymorphisms in PLAU promoter were -25 C/T （rs2227579） and 43 G/T （rs2227580）. Detection of these promoter polymorphisms revealed significant differences in allele and genotype frequency for -25 CfT and 43 G/T

关键词： PLAU gene promoter Alzheimer＇s disease polymorphism

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