检索结果-南通市图书馆

EEG/ERP evidence of possible hyperexcitability in older adults with elevated beta-amyloid

在线全文

学校读者我要写书评

暂无评论

Translational Neurodegeneration 2022年第1期11卷 835-844页

作者： Hannes Devos Kathleen Gustafson Ke Liao Pedram Ahmadnezhad Bradley Estes Laura E.Martin Jonathan D.Mahnken William M.Brooks Jeffrey M.Burns Department of Physical Therapy Rehabilitation Scienceand Athletic TrainingUniversity of Kansas Medical CenterKansas CityKS 66160USA Department of Neurology University of Kansas Medical CenterKansas CityKS 66160USA Hoglund Biomedical Imaging Center University of Kansas Medical CenterKansas CityKS 66160USA Department of Population Health University of Kansas Medical CenterKansas CityKS 66160USA Department of Biostatistics and Data Science University of Kansas Medical CenterKansas CityKS 66160USA University of Kansas Alzheimer’s Disease Center University of Kansas Medical CenterKansas CityKS 66160USA.

Background: Although growing evidence links beta-amyloid (Aβ) and neuronal hyperexcitability in preclinical mouse models of Alzheimer’s disease (AD), a similar association in humans is yet to be established. The first aim of the study was to determine the association between elevated Aβ (Aβ+) and cognitive processes measured by the P3 event-related potential (ERP) in cognitively normal (CN) older adults. The second aim was to compare the event- related power between CNAβ+ and CNAβ−. Methods: Seventeen CNAβ+ participants (age: 73 ± 5, 11 females, Montreal Cognitive Assessment [MoCA] score 26 ± 2) and 17 CNAβ- participants group-matched for age, sex, and MOCA completed a working memory task (n-back with n = 0, 1, 2) test while wearing a 256-channel electro-encephalography net. P3 peak amplitude and latency of the target, nontarget and task difference effect (nontarget−target), and event-related power in the delta, theta, alpha, and beta bands, extracted from Fz, Cz, and Pz, were compared between groups using linear mixed models. P3 ampli-tude of the task difference effect at Fz and event-related power in the delta band were considered main outcomes. Correlations of mean Aβ standard uptake value ratios (SUVR) using positron emission tomography with P3 amplitude and latency of the task difference effect were analyzed using Pearson Correlation Coefficient r. Results: The P3 peak amplitude of the task difference effect at Fz was lower in the CNAβ+ group (P = 0.048). Simi-larly, power was lower in the delta band for nontargets at Fz in the CNAβ+ participants (P = 0.04). The CNAβ+ partici-pants also demonstrated higher theta and alpha power in channels at Cz and Pz, but no changes in P3 ERP. Strong correlations were found between the mean Aβ SUVR and the latency of the 1-back (r = − 0.69;P = 0.003) and 2-back (r = − 0.69;P = 0.004) of the task difference effect at channel Fz in the CNAβ+ group. Conclusions: Our data suggest that the elevated amyloid in cognitively normal ol

关键词： Event-related potentials Electro-encephalography Working memory Older adults Preclinical beta-amyloid

Spatial structure of beta-amyloid Aβ_(1-40) in complex with a biological membrane model

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Advances in Alzheimer's Disease 2012年第3期1卷 22-29页

作者： Konstantin SUsachev Andrey VFilippov Oleg NAntzutkin Vladimir VKlochkov Kazan Federal University KazanRussia Lulea University of Technology LuleaSweden Department of Physics Warwick UniversityCoventryUK

The spatial structure of beta-amyloid Aβ1-40 in complex with sodium dodecyl sulfate micelles as a model membrane system was investigated by 1H-1H two-dimensional NMR (TOCSY, NOESY) spectroscopy and molecular dynamic method calculations. On the basis of NOE and chemical shifts changes data, spatial structure of the complex beta-amyloid-model of the cell surface membrane was obtained.

关键词： 1H NMR Two-Dimensional NMR (TOCSY NOESY) Spectroscopy Alzheimer’s Disease beta-amyloid Oligopeptides Micelle

A lysosome-targeting dual-functional fluorescent probe for imaging intracellular viscosity and beta-amyloid

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

A lysosome-targeting dual-functional fluorescent probe for i...

Balance of synaptic and extrasynaptic NMDA receptors play an important role in beta-amyloid induced neurotoxicity

第十一届全国化学生物学学术会议

作者： Jinsheng Liu Hui-ya Tan Jinwu Yan School of Biology and Biological Engineering South China University of Technology

A lysosome-targeting dual-functional fluorescent probe was rationally designed and developed for imaging intracellular lysosomal viscosity and beta-amyloid. Neutral merocyanine dye（MC-1） was selected as the fluorophore to design probe Lyso-MC, In our study, a 3-morpholinopropylamine moiety was rationally introduced as an electron-donor to enhance the π electron conjugation so as to improve the fluorescence quantum yield, and function as a lysosomal targeting group. Lyso-MC exhibited an excellent linear relationship between the logarithm of fluorescence intensity and the logarithm of viscosity（R2 = 0.99, x = 0.53）. Meanwhile, the probe also showed a significant turn-on fluorescence response when bound to Aβ aggregates and a high sensitivity towards Aβ aggregates（detection limit: 10.2 nM）. Besides this, Lyso-MC was applied to monitor lysosomal viscosity changes and detect intracellular Aβ aggregates. More importantly, the real-time tracking of the dynamic movement of lysosomes, as vesicle structures, was achieved using Lyso-MC. Taking advantage of its remarkable properties, this versatile probe could be a promising imaging tool for use in Alzheimer’s disease pathology-related fields.

关键词： dual-functional fluorescent probe lysosomal viscosity beta-amyloid

来源： cnki会议评论

在线全文

cnki会议

学校读者我要写书评

暂无评论

中国药理学与毒理学杂志 2019年第10期 845-845页

作者： HUANG Yan SHEN Wei LIU Gang ZHANG Yong-Xiang ZHOU Wen-Xia Beijing Institute of Pharmacology and Toxicology State Key Laboratory of Toxicology and Medical Countermeasures

OBJECTIVE Alzheimer disease(AD)patients suffer a disturbance in the balance between synaptic NMDARs(NR2A, mediating the protective pathway)and extrasynaptic NMDARs(NR2B, mediating the excitotoxic pathway), and this study aim to find out whether restoring the balance of NR2A and NR2B is beneficial for AD. METHODS Aβ treated hippocampal slices and Aβicv injection animals were used as AD models in this study. Long-term potentiation(LTP) and behavior test were used to evaluate the effects of drugs and signal pathways were analyzed by Western blotting. RESULTS Specific activation of NR2A and inhibition of NR2B showed the best protective effect against Aβ-induced long-term potentiation(LTP) deficits. In Aβ icv injection animals, the combination of ifenprodil and D-cycloserine(a co-activator of NMDRs similar to D-serine) showed better protective effects against Aβ-induced cognitive deficits(nest building, novel object recognition and Morris water maze) than ifenprodil or D-cycloserine alone. The ratio of NR2A to NR2B, TORC dephosphorylation and ERK1/2 activation(which could be initiated by NR2A) decreased in the hippocampal tissues of Aβ-treated animals. As a result, the activation of CREB and the content of brainderived BDNF decreased. The combination of ifenprodil and D-cycloserine showed the best protective effects,indicating that Aβ-induced toxicology was mediated both by inhibiting NR2A and enhancing NR2B. CONCLUSION These results indicate that enhancing synaptic NMDARs and inhibiting extrasynaptic NMDARs concurrently showed good effects against Aβ-induced neurotoxicity,suggesting that modulation of the balance between NR2A and NR2B could be a potential strategy for AD drug development and therapy.

关键词： beta-amyloid NR2A NR2B balance Alzheimer disease

抗beta-amyloid寡聚体单链可变区抗体的研究

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

抗Beta-Amyloid寡聚体单链可变区抗体的研究

Liposome based drug delivery as a potential treatment option for Alzheimer’s disease

中国神经科学学会第四次会员代表大会暨第七届全国学术会议

作者：刘喆刘瑞田清华大学医学院

越来越多的研究表明,引起阿兹海默病(AD)的关键因素是体积较小的beta-amyloid(Aβ)寡聚体,而非Aβ单体和纤维状聚合物。几年前,曾寄予巨大希望用于治疗AD的A-beta疫苗因可引起严重副作用而被迫停止试验。为了消除疫苗的副作用,我们应用... 详细信息

越来越多的研究表明,引起阿兹海默病(AD)的关键因素是体积较小的beta-amyloid(Aβ)寡聚体,而非Aβ单体和纤维状聚合物。几年前,曾寄予巨大希望用于治疗AD的A-beta疫苗因可引起严重副作用而被迫停止试验。为了消除疫苗的副作用,我们应用噬菌体显示技术从人源化抗体库筛选并鉴定出了7株抗Aβ寡聚体的单链可变区抗体(scFv),并对其生物功能进行了体外测定。scFv具有分子量较小,易穿透生物屏障,其基因较易进行基因工程操作等优点。通过本实验研究希望能为AD的临床治疗提供具有良好应用前景的制剂。

关键词：阿尔兹海默病 beta-amyloid 寡聚体单链可变区抗体

来源： cnki会议评论

在线全文

cnki会议

学校读者我要写书评

暂无评论

Neural Regeneration Research 2022年第6期17卷 1190-1198页

作者： Carely Hernandez Surabhi Shukla Department of Pharmaceutical Sciences College of PharmacyLarkin UniversityMiamiFLUSA

Alzheimer’s disease is a neurodegenerative condition leading to atrophy of the brain and robbing nearly 5.8 million individuals in the United States age 65 and older of their cognitive ***’s disease is associated with dementia and a progressive decline in memory,thinking,and social skills,eventually leading to a point that the individual can no longer perform daily activities *** available drugs on the market temporarily alleviate the symptoms,however,they are not successful in slowing down the progression of Alzheimer’s *** and cures have been constricted due to the difficulty of drug delivery to the blood-brain *** studies have led to identification of vesicles to transport the necessary drugs through the blood-brain barrier that would typically not achieve the targeted area through systemic delivered ***,liposomes have emerged as a viable drug delivery agent to transport drugs that are not able to cross the blood-brain *** are being used as a component of nanoparticle drug delivery;due to their biocompatible nature;and possessing the capability to carry both lipophilic and hydrophilic therapeutic agents across the blood brain barrier into the brain *** indicate the importance of liposomal based drug delivery in treatment of neurodegenerative *** idea is to encapsulate the drugs inside the properly engineered liposome to generate a response of *** are engineered to target specific diseased moieties and also several surface modifications of liposomes are under research to create a clinical path to the management of Alzheimer’s *** review deals with Alzheimer’s disease and emphasize on challenges associated with drug delivery to the brain,and how liposomal drug delivery can play an important role as a drug delivery method for the treatment of Alzheimer’s *** review also sheds some light on variation of ***

关键词： Alzheimer’s disease beta-amyloid blood-brain barrier brain delivery drug delivery systems encapsulated drugs liposomes nanoparticles neurodegenerative diseases PEGylation targeted delivery tau

Can mouse models mimic sporadic Alzheimer’s disease?

在线全文

学校读者我要写书评

暂无评论

Neural Regeneration Research 2020年第3期15卷 401-406页

作者： Bettina M.Foidl Christian Humpel Laboratory of Psychiatry and Experimental Alzheimer’s Research Medical University of Innsbruck

Alzheimer’s disease(AD)is a progressive neurodegenerative disorder and the most common form of dementia *** age is the main risk factor,>97%of all AD cases are of sporadic origin,potentiated by various risk factors associated with life style and starting at an age>60 ***amyloid precursor protein or Presenilins 1 or 2,and symptoms already start at an age<30 *** order to study progression of AD,as well as therapeutic strategies,mouse models are *** far many transgenic mouse models have been developed and used,with mutations in the APP or presenilin or combinations(3×Tg,5×Tg).However,such transgenic mouse models more likely mimic the genetic form of AD and no information can be given how sporadic forms *** risk genes,such as Apolipoprotein E4 and TREM-2 enhance the risk of sporadic AD,but also many risk factors associated with life style(e.g.,diabetes,hypercholesterolemia,stress)may play a *** this review we discuss the current situation regarding AD mouse models,and the problems to develop a sporadic mouse model of AD.

关键词： Alzheimer’s disease beta-amyloid cerebral amyloid angiopathy cognitive impairment sporadic and genetic mouse models tau vascular risk factors

Exosomes: a novel therapeutic target for Alzheimer's disease?

在线全文

学校读者我要写书评

暂无评论

Neural Regeneration Research 2018年第5期13卷 930-935页

作者： Zhi-You Cai Ming Xiao Sohel H.Quazi Zun-Yu Ke Department of Neurology Chongqing General Hospital Department of Anatomy Nanjing Medical University Department of Biological and Health Sciences Texas A & M University-Kingsville Department of Neurology Renmin Hospital Hubei University of Medicine

Extracellular exosomes are formed inside the cytoplasm of cells in compartments known as multivesicular bodies. Thus, exosomes contain cytoplasmic content. Multivesicular bodies fuse with the plasma membrane and release exosomes into the extracellular environment. Comprehensive research suggests that exosomes act as both inflammatory intermediaries and critical inducers of oxidative stress to drive progression of Alzheimer＇s disease. An important role of exosomes in Alzheimer＇s disease includes the formation of neurofibrillary tangles and beta-amyloid production, clearance, and accumulation. In addition, exosomes are involved in neuroinflammation and oxidative stress, which both act as triggers for beta-amyloid pathogenesis and tau hyperphosphorylation. Further, it has been shown that exosomes are strongly associated with beta-amyloid clearance. Thus, effective measures for regulating exosome metabolism may be novel drug targets for Alzheimer＇s disease.

关键词： nerve regeneration microvesicle beta-amyloid tau neuroinflammation oxidative stress therapeutic target neurodegeneration dementia neural regeneration

Peripheral clearance of brain-derived Aβ in Alzheimer's disease: pathophysiology and therapeutic perspectives

在线全文

学校读者我要写书评

暂无评论

Translational Neurodegeneration 2020年第2期9卷 178-188页

作者： Yuan Cheng Ding-Yuan Tian Yan-Jiang Wang Department of Neurology and Centre for Clinical Neuroscience Daping HospitalThird Military Medical UniversityChongqingChina The Institute of Brain and Intelligence Third Military Medical UniversityChongqingChina Key Laboratory of Aging and Brain Diseases ChongqingChina Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesShanghaiChina

Alzheimer’s disease(AD)is the most common type of dementia,and no disease-modifying treatments are available to halt or slow its ***-beta(Aβ)is suggested to play a pivotal role in the pathogenesis of AD,and clearance of Aβfrom the brain becomes a main therapeutic strategy for *** studies found that Aβclearance in the periphery contributes substantially to reducing Aβaccumulation in the ***,understanding the mechanism of how Aβis cleared in the periphery is important for the development of effective therapies for *** this review,we summarized recent findings on the mechanisms of Aβefflux from the brain to the periphery and discuss where and how the brain-derived Aβis cleared in the *** on these findings,we propose future strategies to enhance peripheral Aβclearance for the prevention and treatment of *** review provides a novel perspective to understand the pathogenesis of AD and develop interventions for this disease from a systemic approach.

关键词： Alzheimer's disease beta-amyloid Blood-brain barrier Lymphatic vessel Venous sinus Periphery Liver Kidney Intestine Skin Blood Monocyte Enzymes