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Association of creatine kinase with alzheimer’s.dis.as. pathology:A cross-sectional study

Chinese Medical Journal 2024年第1期137卷 117-119页

作者： Yutong Wang Peiyang Gao Hongman Liu Tingyu Wang Jiaming Fan Tingbo Jiang alzheimer’s.dis.as. neuroimaging initiative(ADNI) Beijing Hospital National Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100005China Department of Cardiology The First Affiliated Hospital of Soochow UniversitySuzhouJiangsu 215000China Institute for Cardiovascular science of soochow University SuzhouJiangsu 215000China Department of Neurology Qingdao Municipal HospitalQingdao UniversityQingdaoShandong 266071China Cardiac Function Department the Affiliated Taian City Central Hospital of Qingdao UniversityTaianShandong 271000China Department of Cardiac surgery The First Affiliated Hospital of Soochow UniversitySuzhouJiangsu 215000China 不详

To the Editor:Creatine kinase(CK),also called creatine phosphokinase,is primarily located in the cytoplasm and *** can be used to diagnose cardiac diseases such as myocardial infarction,viral myocarditis,and pericarditis because it is a vital kinase directly related to intracellular energy operation,muscle contraction,and adenosine triphosphate(ATP)*** studies have confirmed in recent years that serum biomarkers such as elevated CK are associated with alzheimer’s.dis.as.(AD)and its related pathological protein.[1]Previous research indicated that systemic conditions,particularly cardiovascular and cerebrovascular diseases,are significant risk factors for cognitive impairment,and dysfunction of peripheral organs may also contribute to cognitive decline and AD.[2]However,the connection between CK and AD remains ***,to investigate the association between CK and cerebrospinal fluid(CsF)AD pathology biomarkers,we analyzed data from the alzheimer’s.dis.as. neuroimaging initiative(ADNI),a global multi-centered database.

关键词： alzheimer pathology organs

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Adaptive structured sparse multiview canonical correlation analysis for multimodal brain imaging association identification

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science China(Information sciences) 2023年第4期66卷 212-227页

作者： Lei DU Huiai WANG Jin ZHANG shu ZHANG Lei GUO Junwei HAN the alzheimer's.dis.as. neuroimaging initiative school of Automation Northwestern Polytechnical University school of Computer science Northwestern Polytechnical University

Multimodal brain imaging data can be obtained conveniently through rapidly advancing neuroimaging techniques. These multimodal data, which characterize the brain from distinct perspectives, offer a rare opportunity to comprehensively understand the neuropathology of complex brain disorders. Thus,identifying hidden relationships among multimodal brain imaging data is essential and meaningful. The pairwise correlation between two imaging modalities has been extensively studied. However, the multi-way association among more than three modalities remains unclear and is highly challenging. The difficulty and indeterminacy are largely due to the loss imbalances caused by multiple modalities fusion and the lack of reasonable consideration of the relationship implicated in different brain areas. To address both issues, we propose a structured sparse multiview canonical correlation analysis(sMCCA) with adaptive loss balancing and a novel graph-group penalty. The adaptive loss balancing technique encourages sMCCA to fairly optimize each sub-objective. The graph-group constraint penalizes the brain's regions of interest(ROIs)hierarchically with different regularizations at different levels. We derive an efficient algorithm and present its convergence. Experimental results on synthetic and real neuroimaging data confirm that, compared with state-of-the-art methods, our method is a better alternative as it identifies higher or comparable correlation coefficients and better canonical weights. Importantly, delivered by the canonical weights, the identified ROIs of each modality show a high correlation to each other and brain disorders, which demonstrates the potential of our method for untangling the intricate relationship among multimodal brain imaging data.

关键词： multimodal brain imaging correlation sparse multiview canonical correlation analysis task imbalance adaptive loss balancing graph-group penalty

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Cortical and subcortical Grey Matter Abnormalities in White Matter Hyperintensities and subsequent Cognitive Impairment

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Neuroscience Bulletin 2021年第6期37卷 789-803页

作者： Wenhao Zhu Hao Huang shiqi Yang Xiang Luo Wenzhen Zhu shabei Xu Qi Meng Chengchao Zuo Yong Liu Wei Wang alzheimer’s.dis.as. neuroimaging initiative Department of Neurology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Radiology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Brainnetome Center and National Laboratory of Pattern Recognition Institute of AutomationChinese Academy of SciencesBeijing 100190China school of Artificial Intelligence Beijing University of Posts and TelecommunicationsBeijing 100876China University of the Chinese Academy of sciences Beijing 100049China 不详

Grey matter(GM)alterations may contribute to cognitive decline in individuals with white matter hyperintensities(WMH)but no consensus has yet ***,we investigated cortical thickness and grey matter volume in 23 WMH patients with mild cognitive impairment(WMH-MCI),43 WMH patients without cognitive impairment,and 55 healthy *** WMH groups showed GM atrophy in the bilateral thalamus,fronto-insular cortices,and several parietal-temporal regions,and the WMH-MCI group showed more extensive and severe GM *** GM atrophy in the thalamus and fronto-insular cortices was associated with cognitive decline in the WMH-MCI patients and may mediate the relationship between WMH and cognition in WMH ***,the main results were well replicated in an independent dataset from the alzheimer's.dis.as. neuroimaging initiative database and in other control *** comprehensive results provide robust evidence of specific GM alterations underlying WMH and subsequent cognitive impairment.

关键词： White matter hyperintensities Cognitive impairment Cortical thickness Grey matter volume Replication

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Cerebrospinal fluid phosphorylated tau,visinin-like protein-1,and chitinase-3-like protein 1 in mild cognitive impairment and alzheimer’s.dis.as.

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Translational Neurodegeneration 2018年第1期7卷 221-232页

作者： Hua Zhang Kok Pin Ng Joseph Therriault Min su Kang Tharick APascoal Pedro Rosa-Neto serge Gauthier the alzheimer’s.dis.as. neuroimaging initiative Department of Neurology the First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Neurology National Neuroscience InstituteSingaporeSingapore The McGill University Research Centre for studies in Aging McGill UniversityMontrealCanada 不详

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,*** tau(p-tau)reflects the neuropathology of alzheimer’s.dis.as.(AD)and is useful as diagnostic markers for ***,it is unknown whether these biomarkers have similar or complementary information in ***:We stratified 121 participants from the alzheimer’s.dis.as. neuroimaging initiative(ADNI)database into cognitively normal(CN),stable mild cognitive impairment(sMCI),progressive MCI(pMCI),and dementia due to *** of covariance(ANOVA)and chi-square analyses,spearman correlation,and logistic regression models were performed to test the demographic,associations between biomarkers,and diagnostic accuracies,*** mixed-effects models were used to evaluate the effects of CsF amyloid-β(Aβ)on above biomarkers within diagnostic groups,the combination of diagnostic group and Aβstatus as predictor,and CsF biomarkers as predictors of AD features,including cognition measured by Mini–Mental state Examination(MMsE)and brain structure and white matter hyperintensity(WMH)measured by magnetic resonance imaging(MRI).Results:P-tau,VILIP-1,and YKL-40 were all predictors of AD diagnosis,but combinations of biomarkers did not improve the diagnostic accuracy(AUC 0.924 for p-tau,VILIP-1,and YKL-40)compared to p-tau(AUC 0.922).P-tau and VILIP-1 were highly correlated(r=0.639,pstrongly associated with Aβpathology across clinical stages of AD,while YKL-40 was correlated with Aβpathology in CN and AD ***-1 was associated with acceleration of cognitive decline,hippocampal atrophy,and expansion of ventricles in longitudinal ***-40 was associated with hippocampal atrophy at baseline and follow-up,while p-tau was only associated with worsening WMH at ***:CsF levels of p-tau,VILIP-1,and YKL-40 may have uti

关键词： alzheimer’s disease Amyloid-β Chitinase-3-like protein 1 Phosphorylated tau Visinin-like protein-1

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Genetic profiles of familial late-onset alzheimer’s.dis.as. in China:The shanghai FLOAD study

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Genes & diseases 2022年第6期9卷 1639-1649页

作者： Xin-Yi Xie Qian-Hua Zhao Qiang Huang a Eric Dammer sheng-di Chen Ru-Jing Ren Gang Wang the alzheimer’s.dis.as. neuroimaging initiative Department of Neurology and Institute of Neurology Ruijin Hospital Affiliated with Shanghai JiaoTong University School of MedicineShanghai 200025PR China Institute of Neurology Huashan HospitalFudan UniversityShanghai 200040PR China National Clinical Research Center for Aging and Medicine Huashan HospitalFudan UniversityShanghai 200040PR China Department of Biochemistry Center for Neurodegenerative DiseaseEmory University School of MedicineAtlantaGA 30322USA

Compared with early-onset familial AD(FAD),the heritability of most familial lateonset alzheimer’s.dis.as.(FLOAD)cases still remains ***,there are few reported genetic profiles of FLOAD to *** the present study,targeted sequencing of selected candidate genes was conducted for each of 90 probands with FLOAD and 101 unrelated matched normal controls among Chinese Han *** show a significantly lower rate of mutation in APP and PsENs,and APOE e4 genetic risk is higher for *** the Chinese FLOAD population,the most frequent variant was CR1 rs116806486[5.6%,95%CI(1.8%,12.5%)],followed by coding variants of TREM2(4.4%,95%CI(1.2%,10.9%))and novel mutations of ACE[3.3%,95%CI(0.7%,9.4%)].Next,we found that novel pathogenic mutations in ACE including frame-shift and nonsense mutations were in association with FLOAD regardless of APOE e4 *** from the alzheimer’s.dis.as. neuroimaging initiative(ADNI)database also supported this finding in different *** of in vitro analysis suggest that frame-shift and nonsense mutations in ACE may be involved in LOAD through decreased ACE protein levels without affecting direct processing of APP.

关键词： ACE alzheimer’s.dis.as. Familial late-onset alzheimer’s.dis.as. Gene Mutation

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阿尔茨海默病患者体质指数与中脑边缘多巴胺系统及认知功能的相关性研究

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阿尔茨海默病及相关病杂志 2024年第1期7卷 7-15页

作者：李沁詹杰红廖紫璇李小凤重庆医科大学附属第二医院神经内科重庆400010 邻水县人民医院神经内科四川广安638500

目的:中脑边缘多巴胺系统在体重调节和认知功能中发挥着重要作用。研究发现阿尔茨海默病(alzheimer's.dis.as.,AD)患者的体质指数(body mass index,BMI)和中脑多巴胺边缘系统易受AD病理的影响而发生变化。迄今为止,AD患者的BMI与中脑边... 详细信息

目的:中脑边缘多巴胺系统在体重调节和认知功能中发挥着重要作用。研究发现阿尔茨海默病(alzheimer's.dis.as.,AD)患者的体质指数(body mass index,BMI)和中脑多巴胺边缘系统易受AD病理的影响而发生变化。迄今为止,AD患者的BMI与中脑边缘多巴胺系统的关系尚不清楚。本文旨在探讨AD患者的BMI与中脑边缘多巴胺系统及认知功能的关系。方法:本研究使用的数据来自国际阿尔茨海默病神经影像计划数据库ADNI(alzheimer's.dis.as. neuroimaging initiative, ADNI),所有受试者于基线时进行了Aβ PET成像,同期完成脑核磁扫描及成套神经心理学测评。根据Aβ PET的标准化摄取值比(sUVR)将受试者分为Aβ阳性组(sUVR> 1.11)和阴性组(sUVR≤1.11)。以海马、杏仁核、伏隔核、尾状核和壳核作为中脑边缘多巴胺系统的感兴趣区进行分析。结果:共纳入1182例受试者,其中Aβ阳性608例,Aβ阴性574例。与Aβ阴性组相比,Aβ阳性组的海马、杏仁核、伏隔核及壳核的体积更小,BMI较低(P0.05)。随访分析也表明在Aβ阳性组中,BMI与海马、杏仁核、伏隔核、壳核的体积及认知功能呈正相关。结论:BMI较低的AD患者中脑边缘多巴胺系统体积较小,认知功能较差。

关键词：阿尔茨海默病体质指数认知功能中脑边缘多巴胺系统

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Aberrant functional connectivity network in subjective memory complaint individuals relates to pathological biomarkers

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Translational Neurodegeneration 2018年第1期7卷 275-284页

作者： Kaicheng Li Xiao Luo Qingze Zeng Yeerfan Jiaerken Xiaojun Xu Peiyu Huang Zhujing shen Jingjing Xu Chao Wang Jiong Zhou Min-Ming Zhang the alzheimer’s.dis.as. neuroimaging initiative Department of Radiology 2nd Affiliated Hospital of Zhejiang University School of MedicineNo.88 Jie-fang RoadShang-cheng DistrictHangzhou 310009China Department of Neurology 2nd Affiliated Hospital of Zhejiang University School of MedicineZhejiangChina 不详

Background:Individuals with subjective memory complaints(sMC)feature a higher risk of cognitive decline and clinical progression of alzheimer’s.dis.as.(AD).However,the pathological mechanism underlying sMC remains *** aimed to assess the intrinsic connectivity network and its relationship with AD-related pathologies in sMC ***:We included 44 sMC individuals and 40 normal controls who underwent both resting-state functional MRI and positron emission tomography(PET).Based on graph theory approaches,we detected local and global functional connectivity across the whole brain by using degree centrality(DC)and eigenvector centrality(EC)***,we analyzed amyloid deposition and tauopathy via florbetapir-PET imaging and cerebrospinal fluid(CsF)*** voxel-wise two-sample T-test analysis was used to examine between-group differences in the intrinsic functional network and cerebral amyloid ***,we correlated these network metrics with pathological ***:The sMC individuals showed higher DC in the bilateral hippocampus(HP)and left fusiform gyrus and lower DC in the inferior parietal region than *** all subjects,the DC of the bilateral HP and left fusiform gyrus was positively associated with total tau and phosphorylated ***,no significant between-group difference existed in EC and cerebral amyloid ***:We found impaired local,but not global,intrinsic connectivity networks in sMC *** the relationships between DC value and tau level,we hypothesized that functional changes in sMC individuals might relate to pathological biomarkers.

关键词： subjective memory complaint Functional connectivity Graph theoretical analysis Neuropathology Eigenvector centrality Degree centrality

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MR影像体素形态学的阿尔茨海默病自动分类方法

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东南大学学报（自然科学版） 2015年第2期45卷 260-265页

作者：郭圣文池敏越岑桂英匡翠立牛传筱赖春任吴效明 The alzheimer's.dis.as. neuroimaging initiative (ADNI) 华南理工大学材料科学与工程学院广州510006

为了确定轻度认知功能障碍(MCI)与阿尔茨海默病(AD)患者发生萎缩的重要脑区,实现正常老年人(NC)对照组、MCI与AD三组人群的分类,选择了178名被试的脑部MR影像,利用体素形态学与方差分析方法,考察NC,MCI与AD三组人群的MR影像中灰质体积差... 详细信息

为了确定轻度认知功能障碍(MCI)与阿尔茨海默病(AD)患者发生萎缩的重要脑区,实现正常老年人(NC)对照组、MCI与AD三组人群的分类,选择了178名被试的脑部MR影像,利用体素形态学与方差分析方法,考察NC,MCI与AD三组人群的MR影像中灰质体积差异;然后,采用递归特征消去法对特征进行降维;最后,利用线性支持向量机对这3种人群进行分类.实验结果表明,MCI组与NC组、MCI组与AD组、AD组与NC组的平均分类准确率分别为(90.2±1.3)%,(74.7±0.9)%,100%.对分类产生重要影响的脑区包括海马、海马旁回、杏仁核、梭状回和嗅皮层等.所提方法不仅能有效揭示NC,MCI,AD三组人群的脑灰质差异,阐明MCI患者与AD患者脑区发生萎缩的过程与特性,而且能准确区分这3组人群,具有显著的临床应用价值.

关键词：阿尔茨海默病轻度认知功能障碍体素形态学支持向量机递归特征消除

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Cerebrospinal fluid heart fatty acid-binding protein as a predictive biomarker of neurodegeneration in alzheimer's.dis.as.

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Brain science Advances 2021年第1期7卷 44-55,1-5页

作者： Lu Pan Ya-Nan Ou Lin Tan Lan Tan Jin-Tai Yu alzheimer’s.dis.as. neuroimaging initiative Department of Neurology Qingdao Municipal HospitalDalian Medical UniversityDalian 116044LiaoningChina Department of Neurology Qingdao Municipal HospitalQingdao UniversityQingdao 266071ShandongChina Department of Neurology and Institute of Neurology Huashan HospitalShanghai Medical CollegeFudan UniversityShanghai 200040China 不详

Objective:This study aims to investigate whether the heart fatty acid-binding protein(HFABP)in the cerebrospinal fluid(CsF)was a potential predictive biomarker for alzheimer’s.dis.as.(AD).Methods:We evaluated the associations of CsF HFABP levels with core biomarkers,cognition,and brain structure in a sample population(n=302)from the alzheimer’s.dis.as. neuroimaging initiative(ADNI)*** linear regression and mixed-effects models were employed in the *** progression was assessed using the Kaplan–Meier survival ***:CsF HFABP was higher in patients with mild cognitive impairment and AD than the normal controls(ps particularly higher in those with amyloid-β(Aβ)pathologic *** HFABP was associated with higher baseline CsF t-tau(psF p-tau(psF t-tau/Aβ42 and CsF p-tau/Aβ42(psF HFABP was found to play predictive roles in hippocampal atrophy(psk of AD(psion:Our findings suggest that CsF HFABP can be a predictive biomarker of AD.

关键词： alzheimer’s.dis.as. heart fatty acid-binding protein(HFABP) cerebrospinal fluid biomarker neurodegeneration

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Detection and clearance in alzheimer’s.dis.as.: leading with illusive chemical, structural and morphological features of the targets

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Neural Regeneration Research 2024年第3期19卷 497-498页

作者： Luís Gales i3s−Instituto de Investigação e Inovação em saúde Rua Alfredo AllenPortoPortugal(Gales L)IBMC−Instituto de Biologia Molecular e CelularUniversidade do PortoRua Alfredo AllenPortoPortugal ICBAs−Instituto de Ciências Biomédicas Abel salazar Rua de Jorge Viterbo FerreiraPortoPortugal

Highly specific interactions between biomolecules,such as antigen-antibody,protein-ligand,or nucleic acid base pair complementary are on the basis of the organization of complex *** same principles may be tentatively used in molecular medicine for diagnosis and therapeutics.A molecule can be designed to selectively bind a protease and thereby inhibit the production of a peptide that forms toxic aggregates in the brain or an antibody may be produced to bind specifically to that peptide for detection or clearance ***,interference in biological systems is not that *** a start there is the inhibition of the physiological role of the protease;moreover,several cleavage fragments may be produced,which may continue to diverge due to putative post-translational modification and self-assembly processes,hiding the toxic target in a“soup”of peptide species varying in size,structure and chemical composition.A perspective of the current status and challenges in targeting peptide species for diagnosis and treatment in the context of alzheimer’s.dis.as. is given.

关键词： alzheimer diagnosis thereby

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