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Heparan sulfate proteoglycans as possible diagnostic molecular tools with therapeutic potential in alzheimer′s.dis.as.

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Neural Regeneration Research 2021年第7期16卷 1404-1405页

作者： Iván Fernández-Vega Laura Lorente-Gea Carla Martín Luis M.Quirós Department of Pathology Hospital Universitario Central de Asturias/Biobank of Principality of AsturiasHealth Research Institute of the Principality of AsturiasOviedoSpain Department of Pathology Hospital Universitario de Araba-Txagorritxu/Biobanco Vasco para la Investigación(O+eHun)Brain BankHospital UniversitarioVitoriaSpain Instituto Universitario Fernández-Vega OviedoSpain Department of Functional Biology University of OviedoSpain

Importance of dementia and alzheimer's.dis.as.(AD): On Earth, there is a "country" that we call Dementia with around 50 million inhabitants and an estimated global economic cost of Us $1 trillion(Wimo et al., 2017).AD may contribute to 60–70% of cases, with other major forms of dementia being vascular dementia, dementia with Lewy bodies and a group of diseases that contribute to frontotemporal ***, the boundaries between different forms of dementia are indistinct and mixed forms often co-exist, which are only confirmed after postmortem neuropathological studies(Fernandez-Vega et al., 2015).

关键词： al. diseases alzheimer

The First Pilot Epigenetic Type Improvement of Neuropsychiatric symptoms in a Polymorphic Dopamine D2 (-DRD2/ANKK (Taq1A)), OPRM1 (A/G), DRD3 (C/T), and MAOA (4R) Compromised Preadolescence Male with Putative PANDAs/CANs: Positive Clinical Outcome with Precision-Guided DNA Testing and Pro-Dopamine Regulation (KB220) and Antibacterial Therapies

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Open Journal of Immunology 2024年第3期14卷 60-86页

作者： Kenneth Blum Igor Elman David Han Colin Hanna David Baron Ashim Gupta shan Kazmi Jag Khalsa Debasis Bagchi Thomas McLaughlin Rajendra D. Badgaiyan Edward J. Modestino Drew Edwards Catherine A. Dennen Eric R. Braverman Abdalla Bowirrat Keerthy sunder Kevin Murphy Nicole Jafari Foojan Zeine Paul R. Carney Mark s. Gold Kai-Uwe Lewandowski Alireza sharafshah Aryeh R. Pollack Panayotis K. Thanos Division of Addiction Research & Education Center for Sports and Mental Health Western University of Health Sciences Pomona CA USA Department of Psychiatry Boonshoft School of Medicine Wright State University and Dayton VA Medical Centre Dayton OH USA Division of Nutrigenomics Victory Nutrition International Lederoch PA USA Institute of Psychology ELTE Etvs Lornd University Budapest Hungary Department of Psychiatry School of Medicine University of Vermont Burlington VT USA The Kenneth Blum Behavioral & Neurogenetic Institute LLC. Austin TX USA Department of Molecular Biology Adelson School of Medicine Ariel University Ariel Israel Division of Neuromodulation Research Karma Doctors & Karma TMS Palm Springs CA USA Division of Personalized Interventions Peak Logic Del Mar CA USA Division of Personalized Medicine Cross-Cultural Research & Educational Institute San Clemente CA USA Awareness Integration Institute San Clemente CA USA Division of Personalized Pain Therapy Center for Advanced Spine Care of Southern Arizona Tucson AZ USA Department of Psychiatry Harvard School of Medicine Cambridge MA USA Department of Management science and statistics University of Texas San Antonio TX USA Behavioral Neuropharmacology and neuroimaging Laboratory Clinical Research Institute on Addictions Department of Pharmacology and Toxicology Jacobs School of Medicine and Biomedical Sciences University at Buffalo Buffalo NY USA Future Biologics Lawrenceville GA USA Department of Microbiology Immunology & Tropic Diseases School of Medicine Georgetown University Washington DC USA Department of Pharmaceutical sciences College of Pharmacy Texas Southern University Houston TX USA Department of Psychiatry School of Medicine Case Western University Cleveland OH USA Brain and Behavior Laboratory Curry College Milton MA USA The Neurogenesis Project Jacksonville FL USA Department of Family Medicine Jefferson Health Northeast Philadelphia PA USA Departmen

Pediatric autoimmune neuropsychiatric disorders associated with or without streptococcal and other bacterial infections (PANDAs/CANs) are emerging as a featured pediatric disorder. Although there is some controversy regarding treatment approaches, especially related to the behavioral sequelae, we have hypothesized in other published work that it is characterized by the rapid onset of Reward Deficiency syndrome (RDs) in children. We propose utilizing a multi-systems biological approach involving the coupling of genetic addiction risk testing and pro-dopamine regulation (KB220/POLYGEN®) to help induce “dopamine homeostasis” in patients with PANDAs, especially those with known DNA-induced hypodopaminergia. This case study examines a 12-year-old Caucasian male with no prior psychiatric issues who presented with a sudden onset of severe anxiety, depression, emotional liability, and suicidal ideation. The patient underwent genotyping and the genetic addiction risk score (GARs) testing, which revealed risk polymorphisms in the dopamine D2 (-DRD2/ANKK (Taq1A), OPRM1 (A/G), DRD3 (C/T), and MAOA (4R) genes. These polymorphisms have been linked to hypodopaminergia. The patient was subsequently placed on research ID-KB220ZPBMPOLY (POLYGEN®), and albeit the possibility of bias, based upon self and parental assessment, a marked rapid improvement in psychiatric symptoms was observed. In the second phase of treatment (102 days utilizing KB220), the patient received standard antibody testing, which was positive for Lyme. Antibacterial therapy started immediately, and KB220z was discontinued to provide a wash-out period. A monotonic trend analysis was performed on each outcome measure, and a consistently decreasing trend was observed utilizing antibacterial therapy. Our recommendation, albeit only one case, is to utilize and further research a combined therapeutic approach, involving precision-guided DNA testing and pro-dopamine regulation along with antibacterial therapy, as well as

关键词： PANDAs CANs Genetic Addiction Risk Testing (GARs) Pro-Dopamine Regulation Hypodopaminergia Polymorphisms Antibacterial Therapy Infections

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中国阿尔茨海默病早期预防指南(2024)

阿尔茨海默病及相关病杂志 2024年第3期7卷 168-175页

作者：林璐马辛王刚王虹峥王志群王志稳王晓明王惠芳朱飞奇乔立艳刘肇瑞齐志刚汤彬李坤成李朝辉肖世富郁金泰周显波赵禾欣赵忙所赵红彬顾耘郭红郭玲郭起浩富丽萍雷敏潘伟刚徐勇王军阿尔茨海默病防治协会苏州大学附属第一医院江苏苏州215000 首都医科大学附属北京安定医院北京100032 上海交通大学医学院附属瑞金医院上海200025 北京协和医学院北京100005 航天中心医院影像科北京100049 北京大学护理学院北京100191 川北医学院附属医院四川南充637002 同济大学附属养志康复医院(上海市阳光康复中心) 上海201613 深圳市罗湖区人民医院/深圳大学第三附属医院神经内科广东深圳518005 清华大学玉泉医院北京100040 北京大学第六医院北京100083 首都医科大学宣武医院北京100053 上海剪爱公益发展中心上海201824 郑州大学第一附属医院郑州450052 上海交大医学院附属精神卫生中心上海200025 复旦大学附属华山医院国家神经疾病医学中心上海200040 华盛顿临床研究学院阿尔茨海默研究中心(美国) 阿斯诺来(上海)医药科技有限公司上海200131 北京医院北京100730 上海市中医老年医学研究所上海200031 上海中医药大学附属龙华医院上海200032 北京中医药大学护理学院北京102401 昆明理工大学附属安宁第一人民医院暨昆明市第四人民医院昆明650302 复旦大学附属华山医院上海200040 中日友好医院北京100029 河北医科大学第三医院河北廊坊065799 苏州大学苏州医学院江苏苏州215000 北京交通大学北京100091 阿尔茨海默病防治协会北京100027

阿尔茨海默病是一种病因复杂的严重智力致残疾病,目前尚无有效的治疗方法。我国是世界上老年人口最多、增长最快的国家之一,也是阿尔茨海默病发病率较高的国家。因此,如何早期预防阿尔茨海默病的发生,是现今健康领域最重要的课题之一。... 详细信息

阿尔茨海默病是一种病因复杂的严重智力致残疾病,目前尚无有效的治疗方法。我国是世界上老年人口最多、增长最快的国家之一,也是阿尔茨海默病发病率较高的国家。因此,如何早期预防阿尔茨海默病的发生,是现今健康领域最重要的课题之一。我们在国内外相关研究的基础上,通过文献循证、干预研究实践、案例分析、经验总结和专家咨询,结合中国老年健康和社会文化特点,体现中国传统医学、武术、养生以及社区组织优势,制订出具有中国特色的阿尔茨海默病早期预防指南,涵盖了个人、家庭和社会三个层面的预防策略,从积极生活态度、社会活动参与、认知训练、体育锻炼、戒烟限酒、营养、睡眠,血压、血糖、血脂管理,体重和其他慢病管理以及中医开展针对阿尔茨海默病的一级预防。本指南仅供个人、家庭和社会开展阿尔茨海默病预防时参考。

关键词：阿尔茨海默病早期预防指南

Dementia in military and veteran populations:a review of risk factors—traumatic brain injury,post-traumatic stress disorder,deployment,and sleep

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Military Medical Research 2022年第3期9卷 351-364页

作者： Zara Raza syeda F.Hussain suzanne Ftouni Gershon spitz Nick Caplin Russell G.Foster Renata s.M.Gomes Research and Innovation Blind Veterans UK12-14 Harcourt StreetLondonW1H 4HDUK BRAVO VICTOR Research12-14 Harcourt StreetLondonW1H 4HDUK Circadian Therapeutics OxfordOX11BYUK school of Psychological sciences Monash University18 Innovation WalkClayton CampusWellington RoadMelbourneVIC3800Australia sleep&Circadian Neuroscience Institute(sCNi) Nuffield Department of Clinical NeurosciencesSir William Dunn School of PathologyOxford Molecular Pathology InstituteUniversity of OxfordSouth Parks RoadOxfordOX13RFUK Northern Hub for Veterans and Military Families Research Department of NursingMidwifery and HealthFaculty of Health and Life SciencesNorthumbria UniversityNewcastleNE77XAUK

The military population face a unique set of risk factors that may increase the risk of being diagnosed with *** brain injury(TBI)and post-traumatic stress disorder(PTsD)have a higher prevalence in this group in comparison to the civilian *** delving into the individual relationships between TBI and dementia,and PTsD and dementia,we are able to better explore dementia in the military and veteran *** there are some inconsistencies in results,the TBI-dementia association has become more widely ***-tosevere TBI has been found to increase the risk of being diagnosed with alzheimer’s.dis.as..A correlation between PTsD and dementia has been established,however,whether or not it is a causal relationship remains *** such as blast,combat and chemical exposure may occur during a deployment,along with TBI and/or PTsD diagnosis,and can impact the risk of ***,there is a lack of literature exploring the direct effects of deployment on dementia *** problems have been observed to occur in those following TBI,PTsD and *** sleep has been associated with possible dementia *** limited studies have focused on the link between sleep and dementia in military and veteran populations,sleep is a valuable factor to study due to its association and interconnection with other military/veteran *** review aims to inform of various risk factors to the cognitive health of military members and veterans:TBI,PTsD,deployment,and sleep.

关键词： Dementia alzheimer’s.dis.as. Traumatic brain injury Post-traumatic stress disorder Military Veteran Deployment sleep

Transplantation of bone marrow derived macrophages reduces markers of neuropathology in an APP/Ps1 mouse model

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Translational Neurodegeneration 2019年第1期8卷 412-422页

作者： Luís Costa-Marques Katrin Arnold Marie-Christine Pardon Christiane Leovsky samantha swarbrick Claire Fabian Alexandra stolzing Centre for Biological Engineering School of MechanicalElectrical and Manufacturing EngineeringLoughborough UniversityEpinal WayLoughboroughUK Fraunhofer Institute for Cell Therapy and Immunology LeipzigGermany school of Life sciences Queens Medical CentreUniversity of NottinghamNottinghamUK Leipzig University LeipzigGermany

Background:We investigated early hallmarks of putative therapeutic effects following systemic transplantation of bone marrow derived macrophages(BM-M)in APP/Ps1 transgenic ***:BM-M were transplanted into the tail vein and the animals analysed 1 month ***:BM-M transplantation promoted the reduction of the amyloid beta[37-42]plaque number and size in the cortex and hippocampus of the treated mice,but no change in the more heavily modified pyroglutamate amyloid beta E3 *** number of phenotypically‘small’microglia increased in the *** size decreased overall,indicating a reduction of activated *** expression of interleukin 6 and 10,interferongamma,and prostaglandin E receptor 2 was significantly lower in the hippocampus,while interleukin 10 expression was elevated in the cortex of the treated ***:BM-M systemically transplanted,promote a decrease in neuroinflammation and a limited reversion of amyloid *** exploratory study may support the potential of BM-M or microglia-like cell therapy and further illuminates the mechanisms of action associated with such transplants.

关键词： Amyloid beta Microglia alzheimer’s.dis.as. Cell therapy Neuroinflammation

Impact of the biological definition of alzheimer’s.dis.as. using amyloid, tau and neurodegeneration (ATN):what about the role of vascular changes,inflammation,Lewy body pathology?

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Translational Neurodegeneration 2018年第1期7卷 111-117页

作者： s.Gauthier H.Zhang K.P.Ng T.A.Pascoal P.Rosa-Neto McGill Center for studies in Aging Douglas Mental Health Research InstituteMontrealCanada Department of Neurology The First Affiliated Hospital of Chongqing Medical UniversityChongqingChina Department of Neurology National Neuroscience InstituteSingaporeSingapore

Background:The NIA-AA research framework proposes a biological definition of alzheimer’s.dis.as.,where asymptomatic persons with amyloid deposition would be considered as having this.dis.as. prior to ***: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 *** pathological factors may play a leading or an accelerating role in age-associated cognitive decline,including vascular small vessel disease,neuroinflammation and Lewy Body ***:Research should aim at understanding the interaction between all these factors,rather than focusing on them *** this will lead to a personalized approach to the prevention of brain aging,based on individual biological,genetic and cognitive profiles.

关键词： alzheimer’s.dis.as. Diagnosis Treatment Biomarkers Precision medicine Translational research Brain imaging Database analysis Human volunteer cohorts

GM604 regulates developmental neurogenesis pathways and the expression of genes associated with amyotrophic lateral sclerosis

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Translational Neurodegeneration 2018年第1期7卷 322-345页

作者： William R.swindell Krzysztof Bojanowski Mark s.Kindy Raymond M.W.Chau Dorothy Ko Heritage College of Osteopathic Medicine Ohio UniversityAthensOHUSA sunny Biodiscovery IncSanta PaulaCAUSA Department of Pharmaceutical sciences College of PharmacyUniversity of South FloridaTampaFLUSA James A.Haley VAMC TampaFLUSA Genervon Biopharmaceuticals LLC PasadenaCAUSA

Background:Amyotrophic lateral sclerosis(ALs)is currently an incurable disease without highly effective pharmacological *** peptide drug GM604(GM6 or Alirinetide)was developed as a candidate ALs therapy,which has demonstrated safety and good drug-like properties with a favorable pharmacokinetic ***6 is hypothesized to bolster neuron survival through the multi-target regulation of developmental pathways,but mechanisms of action are not fully ***:This study used RNA-seq to evaluate transcriptome responses in sH-sY5Y neuroblastoma cells following GM6 treatment(6,24 and 48 h).Results:We identified 2867 protein-coding genes with expression significantly altered by GM6(FDRsponses included up-regulation of Notch and hedgehog signaling components,with increased expression of developmental genes mediating neurogenesis and axon *** GM6 treatment(24 and 48 h)altered the expression of genes contributing to cell adhesion and the extracellular ***6 further down-regulated the expression of genes associated with mitochondria,inflammatory responses,mRNA processing and chromatin ***6-increased genes were located near GC-rich motifs interacting with C2H2 zinc finger transcription factors,whereas GM6-decreased genes were located near AT-rich motifs associated with helix-turn-helix homeodomain *** motifs interacted with a diverse network of transcription factors encoded by GM6-regulated genes(sTAT3,HOXD11,HEs7,GLI1).We identified 77 ALs-associated genes with expression significantly altered by GM6 treatment(FDRsis,axon guidance and the intrinsic apoptosis ***:Our findings support the hypothesis that GM6 acts through developmental-stage pathways to influence neuron *** expression responses were consistent with neurotrophic effects,ECM modulation,and activation of the Notch and hedgehog neurodevelopmental *** multif

关键词： alzheimer’s.dis.as. Amyotrophic lateral sclerosis Extracellular matrix,Hedgehog Huntington’s.dis.as. Neurodegenerative disease Notch,Parkinson’s.dis.as. RNA-seq Transcriptome

阿尔茨海默病与帕金森病步态分析的中国专家共识

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中华老年心脑血管病杂志 2021年第11期23卷 1141-1145页

作者：中国老年保健协会阿尔茨海默病分会解放军总医院国家老年疾病临床医学研究中心解恒革彭国平唐毅潘晓东罗本燕不详首都医科大学宣武医院神经内科福建医科大学协和医院神经内科浙江大学医学院附属第一医院神经内科

流行病学调查指出我国阿尔茨海默病(Alz-heimer's.dis.as.,AD)患病总人数近1000万,帕金森病(Parkinson disease,PD)患者总人数近300万[1-2]。AD和PD是最常见的神经系统变性疾病,起病隐匿且早期诊断困难,可导致患者运动、认知功能的障碍... 详细信息

流行病学调查指出我国阿尔茨海默病(Alz-heimer's.dis.as.,AD)患病总人数近1000万,帕金森病(Parkinson disease,PD)患者总人数近300万[1-2]。AD和PD是最常见的神经系统变性疾病,起病隐匿且早期诊断困难,可导致患者运动、认知功能的障碍直至全部能力丧失,我国每年医疗和护理支出达数万亿人民币[3]。

关键词：阿尔茨海默病帕金森病步态淀粉样β肽类正电子发射断层显像术

Neuropsychological features of progranulin-associated frontotemporal dementia: a nested case-control study

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Neural Regeneration Research 2021年第5期16卷 910-915页

作者： Marisa Lima Miguel Tábuas-Pereira Diana Duro João Durães Daniela Vieira Inês Baldeiras Maria Rosário Almeida Isabel santana Neurology Department Centro Hospitalar e Universitário de CoimbraCoimbraPortugal University of Coimbra Faculty of MedicineCoimbraPortugal University of Coimbra Center for Neuroscience and Cell BiologyCoimbraPortugal University of Coimbra Center for Research in Neuropsychology and Cognitive Behavioral Intervention(CINEICC)Faculty of Psychology and Educational SciencesCoimbraPortugal

The distinction between sporadic and genetic behavioural-variant frontotemporal dementia(bvFTD)regarding some neuropsychological(NP)features remains ***,progranulin(GRN)-associated bvFTD frequently presents with early episodic memory impairment and some degree of parietal dysfunction which are supporters of alzheimer’s.dis.as.(AD)*** this context,we aimed to characterize the NP profile of GRN-bvFTD as compared to sporadic-bvFTD and AD in patients with mild dementia(Mini-Mental state Examination score≥17 and Clinical Dementia Rating scale score≤*** identified 21 patients at Centro Hospitalar e Universitário de Coimbra,Portugal with GRN mutations belonging to fifteen different *** our focus was bvFTD variants,FTD-related aphasic forms(3 patients)were *** remaining 18 GRN-bvFTD were further matched with 18 sporadic-bvFTD and 18 AD patients according to disease staging,age and *** patients completed the Mini-Mental state Examination,Montreal Cognitive Assessment(MoCA)and a comprehensive NP assessment *** were converted into *** between groups in individual NP measures and NP domains were assessed through non-parametric tests(Kruskal-Wallis test analysis)and eta squared(ŋ2)was calculated as a measure of effect *** comparisons show that GRN patients have worse performances on verbal retrieval processes(P=0.039,ŋ2=0.110)and visuoconstructive abilities(P=0.039,ŋ2=0.190)than sporadic bvFTD *** compared to AD,GRN patients present a higher impairment in frontal(P=0.001,ŋ2=0.211)and parietal(P=0.041,ŋ2=0.129)measures and a better performance in memory tasks(P=0.020,ŋ2=0.120).sporadic-bvFTD forms are worse than AD in frontal measures(P=0.032,ŋ2=0.200),being better in both memory(P=0.010,ŋ2=0.131)and visuospatial skills(P=0.023,ŋ2=0.231).Considering these results,we conclude that GRN-bvFTD patients present a NP profile that associates the typical patterns of FTD and AD ***

关键词： alzheimer’s.dis.as. behavioral variant frontotemporal dementia cognitive profile frontotemporal dementia genetics memory neuropsychology progranulin visuoconstructive ability