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| 1 | 上海市社区人群阿尔茨海默病与载脂蛋白E基因的关联分析显示文摘目的 探讨上海地区社区老年人群中阿尔茨海默病 (AD)与载脂蛋白E(ApoE)ε4 等位基因之间的关联性。方法 应用聚合酶链反应扩增技术及限制性片断长度多态性技术对上海某一社区的 6 3例AD患者、35例血管性痴呆 (VD)患者、71例可疑痴呆 (QD)患者及 36 9名非痴呆者 (不符合痴呆诊断、认知功能无缺陷者 ,对照组 )的ApoE基因进行分型 ,计算各组基因型频数的分布、基因频率及ApoEε4 基因的剂量 ,对AD与ApoE基因多态性进行了关联分析。结果 (1)AD组中含ApoEε4 基因者比例 (47 6 % )明显高于对照组 (2 0 9% ) ,AD组ApoEε4 基因频率 (2 6 2± 3 9) %明显高于对照组(10 5± 1 1) % ,P均 <0 0 1;(2 )从AD与ApoEε4 基因剂量效应来看 ,随着ApoEε4 基因剂量增加 ,不含ApoEε4 、含 1个和含 2个ApoEε4 的AD患病比率 (分别为 9 3%、2 5 %和 5 0 % )明显上升 ;(3)AD组与对照组比较 ,ApoEε4 基因型的比数比为 2 2 8倍 (P <0 0 5 ) ,其 95 %的可信区间为 1 32~ 3 97,归因危险度为 5 6 %。结论 中国上海社区人群AD的发病与ApoEε4 | 陆峥 江三多 张明园 冯国鄞 Robert Katzman Tsunao Saitok | 2001 | 中华精神科杂志2001，34，1： | 10 |
| 2 | Gut-brain connection: The neuroprotective effects of the anti-diabetic drug liraglutide显示文摘Long-acting glucagon-like peptide-1(GLP-1) analogues marketed for type 2 diabetes(T2D) treatment have been showing positive and protective effects in several different tissues, including pancreas, heart or even brain. This gut secreted hormone plays a potent insulinotropic activity and an important role in maintaining glucose homeostasis. Furthermore, growing evidences suggest the occurrence of several commonalities between T2 D and neurodegenerative diseases, insulin resistance being pointed as a main cause for cognitive decline and increased risk to develop dementia. In this regard, it has also been suggested that stimulation of brain insulin signaling may have a protective role against cognitive deficits. As GLP-1 receptors(GLP-1R) are expressed throughout the central nervous system and GLP-1 may cross the blood-brain-barrier, an emerging hypothesis suggests that they may be promising therapeutic targets against brain dysfunctional insulin signaling-related pathologies. Importantly, GLP-1 actions depend not only on the direct effect mediated by its receptor activation, but also on the gut-brain axis involving an exchange of signals between both tissues via the vagal nerve, thereby regulating numerous physiological functions(e.g., energy homeostasis, glucose-dependent insulin secretion, as well as appetite and weight control). Amongst the incretin/GLP-1 mimetics class of anti-T2 D drugs with an increasingly described neuroprotective potential, the already marketed liraglutide emerged as a GLP-1R agonist highly resistant to dipeptidyl peptidase-4 degradation(thereby having an increased half-life) and whose systemic GLP-1R activity is comparable to that of native GLP-1. Importantly, several preclinical studies showed anti-apoptotic, anti-inflammatory, anti-oxidant and neuroprotective effects of liraglutide against T2 D, stroke and Alzheimer disease(AD), whereas several clinical trials, demonstrated some surprising benefits of liraglutide on weight loss, microglia inhibition, behavior and cognition, and in AD biomarkers. Herein, we discuss the GLP-1 action through the gut-brain axis, the hormone's regulation of some autonomic functions and liraglutide's neuroprotective potential. | Emanuel Monteiro Candeias Inês Carolina Sebastio Susana Maria Cardoso Sónia Catarina Correia Cristina Isabel Carvalho Ana Isabel Plácido Maria Sancha Santos Catarina Resende Oliveira Paula Isabel Moreira Ana Isabel Duarte | 2015 | World Journal of Diabetes2015，6，6： | 9 |
| 3 | 老年性痴呆的早期预防显示文摘老年性痴呆,即阿尔茨海默病(Alzheimer's disease,AD),由德国神经病学家Alzheimer首先报道,人们以他的名字来命名该病。AD是最常见的老年期痴呆,是严重威胁老年人生命健康的主要疾病之一。据流行病学调查研究发现,我国老年性痴呆的患病率呈现不断上升趋势,在20世纪80年代,我国报告的AD患病率为0.07%~0.46%,20世纪90年代为2.9%,2000年则为4.2%。自20世纪70年代以来,对AD在临床、药理、生化和遗传学等方面的研究取得了很大的进展,但至今对其病因和发病机制还未完全阐明,目前尚无彻底治愈的方法,因此早期预防和干预受到重视,一直是研究的热点。近年来对轻度认知功能损害(Mild Cognitive Impairment,MCI)的研究也越来越多,很多学者认为MCI是AD的前驱性疾病.对MCI进行干预有重要意义。 | 薛海波 张明园 | 2005 | 上海精神医学2005，17，B09： | 7 |
| 4 | A 36-week multicenter, randomized, double-blind, placebo-controlled,parallel-group, Phase 3 clinical trial of sodium oligomannate for mild-to-moderate Alzheimer disease显示文摘BACKGROUND New therapies are urgently needed for Alzheimer disease(AD). Sodium oligomannate(GV-971) is a marine-derived oligosaccharide that has been shown to decrease amyloid deposition, reduce neuroinflammation, reconstitute gut microbiota, and improve cognition in animal models of AD. A Phase 3 trial was conducted to assess efficacy and safety of GV-971. METHODS We conducted a Phase 3, double-blind placebo-controlled trial in patients with mild-to-moderate AD. Participants were randomized to receive placebo or GV-971(900 mg) for 36 weeks. The primary outcome was the drug-placebo difference in change from baseline on the 12-item cognitive subscale of the Alzheimer′s Disease Assessment Scale(ADAS-cog12). Secondary endpoints were drug-placebo differences on the Clinician′s Interview-Based Impression of Change(CIBIC+), Alzheimer′s Disease Cooperative Study-Activities of Daily Living(ADCS-ADL) scale, and Neuropsychiatric Inventory(NPI). The effect of GV-971 on the cerebral glucose metabolic rate was examined by 18 Fluorine-FDG PET in a subgroup. Safety and tolerability were monitored. RESULTS 818 participants were randomized, of which 408 were assigned to GV-971 and 410 to placebo. A significant drug-placebo difference in favor of GV-971 was present at each measurement time-point on the ADAS-Cog12. The difference between groups with regard to the change from baseline was-2.15 points(95% confidence interval,-3.07 to-1.23;P<0.0001;effect size 0.531) after 36 weeks treatment. There was a trend towards benefit on CIBIC+(P=0.0588) but not on the ADCS-ADL(P=0.5712), NPI(P=0.8004), or the CMRglu. TEAE incidence77% and 76%, comparable between the two groups. Two deaths occurred in the GV-971 group;these were determined not to be related to GV-971. CONCLUSION GV-971 demonstrated significant efficacy in improving cognition and showed sustained improvement across al observation periods. GV-971 was safe and well tolerated. | XIAO Shi-fu | 2019 | 中国药理学与毒理学杂志2019，33，6： | 7 |
| 5 | Neuroprotective effects of INT-777 against Aβ1-42-induced cognitive impairment, neuroinflammation, apoptosis, and synaptic dysfunction in mice显示文摘OBJECTIVE To investigate the neuroprotective effects of TGR5 agonist INT-777 in the Aβ_(1-42)-treated mouse model of acute neurotoxicity.METHODS Cognitive impairment was induced by single intracerebroventricular injection of aggregated Aβ_(1-42)(410 pmol per mouse;5 μL)into the mouse brain in normal ICR mice.After3 d,INT-777(0.75,1.5 or 3.0 μg per mouse) was infused into the same site.Another 3 d later,the cognition function was evaluated by Morris water maze(MWM),novel objective recognition(NOR),and Y maze tests.Furthermore,the levels of TGR5,TNF-α,IL-1β,IL-6,NF-κB p65,Iba1,caspase 3,Bcl-2,Bax,PSD95,and synaptophysin in the hippocampus and frontal cortex were detected using Western blotting.Microglia activation in the hippocampal CA1,CA3 and DG regions and frontal cortex were detected by immunohistochemistry.TUNEL staining was used to detect the apoptotic cells.The number of spines in the hippocampal CA1,CA3 and DG regions and frontal cortex was detected by GolgiCox staining.RESULTS INT-777(1.5 or 3.0 μg per mouse) significantly ameliorated memory impairment in the Aβ_(1-42)-treated mice,evidenced by increased the time spent in the target quadrant(P<0.05),and the number of target crossings(P<0.05) in the MWM test,increased the discrimination index in the NOR test(P<0.05),and increased the number of correct choices(P<0.05,P<0.01) and decreased the latency(P<0.05) to enter the shock-free compartment in the Y-maze test.Importantly,this treatment reversed Aβ_(1-42)-induced TGR5 down-regulation(P<0.05,P<0.01),suppressed the increase of nuclear NF-κB p65(P<0.05,P<0.01) and mitigated neuroinflammation,evidenced by lower proinflammatory cytokines such as TNF-α(P<0.05),IL-1β(P<0.05),IL-6(P<0.05,P<0.01),and less Iba1-positive cells in the hippocampal CA1,CA3 and DG regions and frontal cortex(P<0.05,P<0.01) as well as the protein level of Iba1.INT-777(1.5 or3.0 μg per mouse) also pronouncedly suppressed apoptosis through the reduction of TUNEL-positive cells(P<0.05,P<0.01),decreased activation of caspase 3(P<0.05),increased ratio of Bcl-2/Bax(P<0.05,P<0.01),and ameliorated synaptic dysfunction via promoting dendritic spines generation(P<0.05,P<0.01) with the upregulation of PSD95(P<0.05) and synaptophysin proteins(P<0.05).CONCLUSION INT-777 has potent neuroprotective effects against Aβ_(1-42)-induced neurotoxicity,which suggests that the activation of TGR5 could be a novel and promising strategy for the treatment of AD. | WU Xian LYU Yang-ge DU Yi-feng CHEN Fang Miranda N REED HU Mei Vishnu SUPPIRAMANIAM TANG Su-su HONG Hao | 2018 | 中国药理学与毒理学杂志2018，32，9： | 6 |
| 6 | 阿尔茨海默病的扩瞳试验研究显示文摘目的 验证扩瞳试验能否用于诊断阿尔茨海默病 (AD)。方法 用非接触型双侧瞳孔红外同步记录分析仪对滴入 0 0 1%托吡卡胺后的瞳孔变化进行测定 ,并自动分析瞳孔直径扩大 (按对照侧校正 )的百分比。共测定AD患者 5 2例、血管性痴呆 (VD)患者 34例、老年精神分裂症 (S) 19例和老年健康人 (对照组 ) 5 7名。比较并找出最能明显区别AD与对照组的瞳孔扩大值 ,以此作为试验结果阳性与否的分界线。结果 AD患者的瞳孔在滴药 7~ 10min后便明显扩大 ,与VD、S或对照组的差异有非常显著性 (P <0 0 1)。如以第 18min时扩大值≥ 15 %作为分界线 ,AD、VD、S及对照组的阳性例数 /总例数分别为 :42 / 5 2、6 / 34、1/ 19和 12 / 5 7;用以诊断AD时的敏感性为 0 81,特异性为0 79~ 0 82 ,一致性Kappa值为 0 6 0~ 0 6 2。结论 扩瞳试验可以作为筛选AD的诊断标志之一 ,也可在鉴别AD与VD时作为参考。 | 项志清 陈月敏 颜文伟 | 2001 | 中华精神科杂志2001，34，1： | 6 |
| 7 | 轻中度晚发型Alzheimer病患者行为和精神症状的调查显示文摘目的了解散发性晚发型阿尔茨海默病(Alzheimer disease,LOAD)的行为和精神症状及其相关因素。方法用相关量表对经诊断的LOAD病人行为和精神症状作详细调查,并对各种行为和精神症状进行分析讨论。结果57.0%的LOAD病人有行为和精神症状,其中行为障碍出现率为42.2%,妄想为33.3%,焦虑为34.62%,抑郁为26.7%,幻觉为17.8%。行为和精神症状出现率与性别、教育程度、病前工作种类及痴呆程度无关。结论LOAD病人的行为和精神症状较为常见,对其细致的观察有利于尽早诊断,及时监护及采取针对性的治疗。 | 江文宇 吕泽平 胡才友 郑陈光 刘文伟 | 2006 | 中国实用神经疾病杂志2006，9，1： | 4 |
| 8 | Acupoint combinations used for treatment of Alzheimer's disease: A data mining analysis显示文摘OBJECTIVE: To identify the acupoint combinations used in the treatment of Alzheimer's disease(AD).METHODS: The clinical literature regarding acupuncture and moxibustion for AD was searched and collected from databases including Chinese Biomedical Medicine, China National Knowledge Infrastructure, Wanfang Database and PubMed. The database of acupuncture and moxibustion prescriptions for AD was established by using Excel software so as to conduct the descriptive analysis, association analysis on the data.RESULTS: Baihui(GV 20), Sishencong(EX-HN 1),Shenmen(HT 7), Zusanli(ST 36), Neiguan(PC 6),Fengchi(GB 20), Taixi(KI 3), Dazhui(GV 14), Shenshu(BL 23), Sanyinjiao(SP 6), Shenting(GV 24), Fenglong(ST 40), Xuanzhong(GB 39), Shuigou(GV 26)and Taichong(LR 3) were of higher frequency in the treatment of AD with acupnucture and moxibustion. Most acupoints were selected from the Governor Vessel. The commonly used acupoints were located on the head, face, neck and lower limbs. The combination of the local acupoints with the distal ones was predominated. The crossing points among the specific points presented the advantage in the treatment. The association analysis indicated that the correlation among Fengchi(GB 20)-Baihui(GV 20) was the strongest, followed by combinations of Dazhui(GV 14)-Baihui(GV 20), Shenshu(BL 23)-Baihui(GV 20) and Neiguan(PC 6)-Baihui(GV 20) and indicated the common rules of the clinical acupoint selection and combination for AD.CONCLUSION: Our findings provide a reference for acupoints selection and combination for AD in clinical acupuncture practice. | Yu Chaochao Wang Li Kong Lihong Shen Feng Ma Chaoyang Du Yanjun Zhou Hua | 2018 | Journal of Traditional Chinese Medicine2018，38，6： | 4 |
| 9 | 阿尔茨海默病的乙酰胆碱酯酶抑制剂治疗显示文摘 | 刘春风 曹勇军 | 2005 | 老年医学与保健2005，11，4： | 4 |
| 10 | Amyloid positron emission tomography and cognitive reserve显示文摘Alzheimer's disease(AD) is characterized by a nonlinear progressive course and several aspects influence the relationship between cerebral amount of AD pathology and the clinical expression of the disease. Brain cognitive reserve(CR) refers to the hypothesized capacity of an adult brain to cope with brain damage in order to minimize symptomatology. CR phenomenon contributed to explain the disjunction between the degree of neurodegeneration and the clinical phenotype of AD. The possibility to track brain amyloidosis(Aβ) in vivo has huge relevance for AD diagnosis and new therapeutic approaches. The clinical repercussions of positron emission tomography(PET)-assessed Aβ load are certainly mediated by CR thus potentially hampering the prognostic meaning of amyloid PET in selected groups of patients. Similarly, amyloid PET and cerebrospinal fluid amyloidosis biomarkers have recently provided new evidence for CR. The present review discusses the concept of CR in the framework of available neuroimaging studies and specifically deals with the reciprocal influences between amyloid PET and CR in AD patients and with the potential consequent interventional strategies for AD. | Matteo Bauckneht Agnese Picco Flavio Nobili Silvia Morbelli | 2015 | World Journal of Radiology2015，7，12： | 3 |
| 11 | Icariin ameliorates learning and memory function via improving cerebral glucose metabolism disorder in APP/PS1/Tau triple transgenic Alzheimer disease mice显示文摘OBJECTIVE To investigate the protective effect of icariin(ICA) on learning and memory function in APP/PS1/Tau triple transgenic Alzheimer disease mice(3×Tg-AD mice),and then to explore whether its mechanism is related to the improvement of brain glucose metabolism disorder.METHODS Three-month-old male 3 ×Tg-AD mice were randomly divided into three groups(n=10):3×Tg group,3×Tg+ICA low-dose group(30 mg·kg-1) and 3×Tg + ICA high-dose group(60 mg·kg-1).Age-matched male wild type(WT) mice were randomly divided into two groups(n=10):WT control group and WT+ICA60 mg·kg-1 group.ICA in vehicle(0.5% Tween-80 in distilled water) was given orally once a day for five months in the 3×Tg+ICA groups.3×Tg and WT control group were given an equal volume vehicle.Morris water maze was used to detect the learning and memory function of mice.Brain glucose metabolism in 3×Tg mice was observed by 18 F-FDG microPET imaging technique.Nissl staining and HE staining were used to evaluate the survival neurons in hippocampus of mice.Glucose oxidase assay was used to detect glucose contents in cortex of mice.The protein expression of APP,Aβ1-40,Aβ1-42 and glucose transporter 1(GLUT1),and the phosphorylation level of tau protein at multiple sites in hippocampus were detected by Western blotting.RESULTS Behavioral examination revealed a profound decrease learning and memory function,accompanied by a decrease in number of neuronal cells in 3×Tg-AD mice.Moreover,the cerebral18 F-FDG uptake rate per gram tissue was reduced and the glucose contents in the cortex were increased in 3×Tg-AD mice.In addition,Western blotting analysis showed that the expression of APP,Aβ1-40,Aβ1-42 proteins and the levels of tau protein phosphorylation at Ser199/202 and PHF-1(Ser396/404) sites were increased significantly,followed by a decrease of GLUT1 expression in hippocampus of 3×Tg-AD mice.All of these changes in behavioral functions,neuronal loss and related protein expression were reversed when mice were treated with ICA.CONCLUSION ICA can improve the learning and memory ability of AD model mice,the mechanism may be related to the improvement of cerebral glucose metabolism dysfunction by increasing the expression of GLUT1. | ZHANG Ying YAN Fei CHEN Mei-xiang JIN Hai NIE Jing SHI Jing-shan JIN Feng | 2018 | 中国药理学与毒理学杂志2018，32，9： | 2 |
| 12 | 阿尔茨海默病发病机理研究进展显示文摘 | 曾雪爱 吴瑞荣 | 2006 | 福建医药杂志2006，28，4： | 2 |
| 13 | 老年性痴呆的预防与治疗显示文摘 | 禹鲁民 胡兴寿 | 2006 | 中国民康医学2006，18，6： | 1 |
| 14 | Shen-Zhi-Ling oral solution improves learning and memory ability in Alzheimer’s disease mouse model显示文摘OBJECTIVE: To investigate the effector mechanisms and effector targets of Shen-Zhi-Ling (SZL) oral solution in the treatment of Alzheimer's disease (AD). METHODS: In this study, we carried out gavage with SZL oral solution in an APP/PS-1 heterozygous double transgenic AD mouse model for 12 continuous weeks. Haematoxylin and eosin staining, Nissl staining and Annexin V/Propidium Iodide staining were used to detect the brain histopathology in AD mouse model. Immunofluorescence staining was used to detect the expression levels of autophagy's proteins. Morris water maze test was used to detect the learning and memory ability in AD mouse model. RESULTS: Pathological results showed that neuronal loss in the hippocampus of mice in the SZL intervention group was significantly alleviated and the number of apoptotic neurons was significantly decreased compared with the control group (physiological saline and non-intervention groups). Immunofluorescence staining results showed that the expression of autophagy activators, Beclin-1 and LC3B, was significantly increased in the hippocampal neurons of mice of the SZL intervention group, while the expression of the apoptotic factor, caspase- 3, was significantly decreased. At the same time, hippocampal accumulation of Aβ42 protein was significantly decreased. In addition, results of the water maze experiment showed that the latency period in mice from the SZL intervention group was significantly reduced. CONCLUSION: In summary, we believe that the SZL oral solution significantly activates autophagy in hippocampal neurons, effectively reducing the accumulation of Aβ42 peptides, alleviating neuronal injury and apoptosis, and ultimately improving the cognitive function in a mouse model of AD. | Chi Huiying Liu Te Pan Weidong Chen Jiulin Wu Beiling Yu Zhihua Chen Chuan | 2019 | Journal of Traditional Chinese Medicine2019，39，5： | 1 |
| 15 | Selective impairment of musical emotion recognition in patients with amnesic mild cognitive impairment and mild to moderate Alzheimer disease显示文摘Background:Patients with Alzheimer disease(AD)and amnesic mild cognitive impairment(aMCI)have deficits in emotion recognition.However,it has not yet been determined whether patients with AD and aMCI also experience difficulty in recognizing the emotions conveyed by music.This study was conducted to investigate whether musical emotion recognition is impaired or retained in patients with AD and aMCI.Methods:All patients were recruited from the First Affiliated Hospital of Anhui Medical University between March 1,2015 and January 31,2017.Using the musical emotion recognition test,patients with AD(n=16),patients with aMCI(n=19),and healthy controls(HCs,n=16)were required to choose one of four emotional labels(happy,sad,peaceful,and fearful)that matched each musical excerpt.Emotion recognition scores in three groups were compared using one-way analysis of variance(ANOVA)test.We also investigated the relationship between the emotion recognition scores and Mini-Mental State Examination(MMSE)using Pearson’s correlation analysis test in patients with AD and aMCI.Results:Compared to the HC group,both of the patient groups showed deficits in the recognition of fearful musical emotions(HC:7.88±1.36;aMCI:5.05±2.34;AD:3.69±2.02),with results of a one-way ANOVA confirming a significant main effect of group(F(2,50)=18.70,P<0.001).No significant differences were present among the three groups for the happy(F(2,50)=2.57,P=0.09),peaceful(F(2,50)=0.38,P=0.09),or sad(F(2,50)=2.50,P=0.09)musical emotions.The recognition of fearful musical emotion was positively associated with general cognition,which was evaluated by MMSE in patients with AD and aMCI(r=0.578,P<0.001).The correlations between the MMSE scores and recognition of the remaining emotions were not significant(happy,r=0.228,P=0.11;peaceful,r=0.047,P=0.74;sad,r=0.207,P=0.15).Conclusion:This study showed that both patients with AD and aMCI had decreased ability to distinguish fearful emotions,which might be correlated with diminished cognitive function. | Shan-Shan Zhou Xin Gao Ya-Juan Hu Yi-Ming Zhu Yang-Hua Tian Kai Wang | 2019 | Chinese Medical Journal2019，，19： | 1 |
| 16 | Effect of Cuzhi liquid on learning and memory dysfunction in a mouse model of Alzheimer's disease显示文摘OBJECTIVE: To examine the effects of Cuzhi liquid on learning and memory abilities in a mouse model of Alzheimer's disease(AD).METHODS: One hundred mice were divided into the normal, AD model, piracetam group, Cuzhi liquid low dose and Cuzhi liquid high dose, each group 20 mice. The AD mouse model was induced by daily intraperitoneal injection of D-galactose and sodium nitrite. AD mice then received intragastric administration of piracetam or Cuzhi liquid for60 d, and changes in learning and memory abilities were assessed using the water maze test. The activity of acetylcholinsterase(AchE) and monamine oxidase(MAO), and the levels of nitrogen monoxidum(NO) and malonaldehyde(MDA), were measured in brain tissues. Amyloid protein deposition was assessed by methyl violet staining, and B-cell lymphoma-2(Bcl-2) expression in the hippocampal cornus ammonis 1 region was detected by immunohistochemistry.RESULTS: In the water maze test, the escape latency of the model group was longer than that of the normal group(P < 0.01). The escape latency of the three using drug treatment groups was significantly less than that of the normal group(P < 0.05). The activity of AchE and MAO, and the levels of NO and MDA, in the brain of the model group were significantly higher than that of the normal group(P <0.01), but significantly reduced in the three drug treatment groups compared with the model group(P < 0.05). AchE activity showed a greater reduction in the two Cuzhi liquid groups compared with the piracetam group(P < 0.01), to levels similar to the normal group. There were no differences in MAO activity or NO levels between the three drug treatment groups, while MDA levels were reduced more in the high-dose Cuzhi liquid group compared with the other treatment groups(P < 0.01). Hippocampal Bcl-2 expression was significantly reduced in the model group compared with the normal group(P < 0.01), but significantly improved in the three drug treatment groups(P < 0.05). The high-dose Cuzhi liquid group showed a significantly greater recovery in Bcl-2 expression compared with the other treatment groups.CONCLUSION: Cuzhi liquid can improve learning and memory impairment in an AD mouse model.The mechanism of action may relate to reduced AchE and MAO activity, and reduced NO and MDA levels, in the brain, and improved Bcl-2 expression,an inhibitor of apoptosis. | Liu Lijuan Yu Chen Liu Junbao | 2018 | Journal of Traditional Chinese Medicine2018，38，6： | 0 |
| 17 | Is tau a suitable therapeutical target in tauopathies?显示文摘Tau is an intracellular protein,found mainly in neurons,but it can also be found in the extracellular space in pathological situations.Here we discuss whether intracellular tau,in aggregated form or modified by phosphorylation,could be toxic inside a neuron.On the other hand,it has been proposed that extracellular tau could be toxic.In this review,we address the question if the elimination of tau would be a possible therapeutic method to avoid tauopathy disorder and we suggest ways to eliminate intracellular and extracellular tau as treatment. | Elena Gomez de Barreda Jesús Avila | 2010 | World Journal of Biological Chemistry2010，1，5： | 0 |
| 18 | Dementia in Taiwan Region显示文摘Objective:Taiwan has an increasing aging population like other developed areas.The aging population will lead to an increased prevalence of dementia.Methods:This article will reflect the status of dementia in Taiwan,including updated epidemiology,diagnosis,subtypes,and optimal treatment of dementia.Results:The article also describes and interprets the Taiwan Dementia Policy to establish a clear,large view of the current state of management of dementia in Taiwan and future policy implementation.Conclusion:A comprehensive policy to dementia,from the basic researches to clinical care and treatment,is necessary to the increased aged population in Taiwan. | Yuanhan Yang | 2016 | Translational Neuroscience and Clinics2016，2，1： | 0 |
| 19 | Physalin B reduce secretion of Aβ by inhibiting phosphorylation of STAT3 via down-regulated expression of β-secretase and γ-secretase显示文摘OBJECTIVE Extracellular amyloid-β(Aβ) plaques are one of the major pathological hallmarks of Alzheimer disease(AD). Therefore, decreasing Aβ levels is one strategyfor preventing the etiology of AD. Aβ peptides are generated from the cleavage of amyloid precursor protein(APP) by the β-secretase(BACE1) and γ-secretase(PS1). Inhibition of these secretases represents an obvious logical strategy to inhibit the generation of Aβ. In addition, signal transducer and activator of transcription 3(STAT3) is known to regulate many genes, and to significantly affect Aβ generation by controlling BACE1 and PS1 expression. Physalin B(PB), one of the major active steroidal constituents of solanaceaephysalis plants, possesses a wide variety of biological activities. PB down-regulates BACE1 and PS1 expression while it is unclear whether PB can regulate Aβ in N2 a/APPswe cells, and if so, whether it is by inhibiting the phosphorylation of STAT3. METHODS N2 a/APPswe cells were treated with PB in different concentrations for 24 h.(1) We used CCK8 method to detect the effects of different concentrations of PB on cell viability, and selected the best concentration for drug treatment to the cells.(2)The contents of Aβ40 and Aβ42 were determined by ELISA.(3) Western blotting was used to detect the expression levels of p-STAT3 and APP metabolism-related proteins, including APP, CTFα, CTFβ, BACE1,PS1, ADAM10 and so on.(4) RT-PCR was performed to detected the m RNA expression of BACE1 and PS1.(5) β-secretase activity Fluorometric assay kit was used to analyzed β-secretase activity.(6) In order to further explore the underlying mechanisms, N2 a/APPswe cells were pre-treated with 100 μmol·L-1 S3 I-201(a STAT3 inhibitor,can effectively prevent STAT3 phosphorylation) for 30 min and then treated with 3 μmol·L-1 PB incubated for 24 h. Then we evaluated the level of expression of STAT3 and p-STAT3 by Western blotting. RESULTS(1) CCK8 experiment results illustrated that PB did not show cytotoxicity at the applied concentration when cells were treated with PB(0, 0.3, 1 and 3 μmol·L-1). So, we used these concentrations in the following experiment.(2) ELISA results showed, compared to the control group, the contents of Aβ40 and Aβ42 decreased with the increasing of PB concentration.(3)According to Western blotting results, PB significant down-regulated the expression of BACE1, PS1, APP, CTFβ and p-STAT3 compared to the control group.(4) RT-PCR results indicated that PB can reduced the m RNA expression of BACE1 and PS1 effectively.(5) It turns out that PB can significantly inhibit BACE1 activity tested by BACE1 activity Fluorometric assay kit.(6) S3 I-201 had a similar manner to significantly inhibited STAT3 phosphorylation with PB through Western blotting. Moreover, co-treated with S3 I-201 and PB inhibited STAT3 phosphorylation much more than treatment with S3 I-201 alone. CONCLUSION These findings indicate that PB can effectively inhibit the expression of BACE1 and PS1 to reduce Aβ secretion by inhibiting the phosphorylation of STAT3. | BAI Shan-shan ZHUO Lin SUN Yi SHI Ru-ling XIE Yong-sheng ZHANG Wei | 2019 | 中国药理学与毒理学杂志2019，33，6： | 0 |
| 20 | Investigation of a Chinese pedigree with early-onset familial Alzheimer’s disease caused by presenilin 1 p.M233T mutation显示文摘Objective To analyze the clinical presentation andgenotype of a Chinese pedigree with early-onset familialAlzheimer's disease. Methods A pedigree with early-onsetfamilial Alzheimer's disease was recruited. The clinicaldata of the proband who was admitted to ShengjingHospital in March 2018 and the family members werecollected. The DNA sequences of 53 dementia relatedgenes were screened using next-generation sequencingtechnology in the blood sample of the proband. The point mutation discovered in the proband was also investigatedin some family members. Results There were five memberswith Alzheimer's disease in the pedigree,includingthe proband,a 42 years old female. The onset age of apedigree member was 33 years and that of the probandwas 37 years. A point mutation from T to C at position698 (M233T) in the exon 7 of presenilin 1 (PS1) genewas found in the proband and two other family memberswho were clinically normal. Conclusion The M233T mutationof PS1 gene can lead to early-onset familialAlzheimer's disease. This family is the first pedigree withM233T mutation of PS1 gene in China,which deservesclinical attention. | 吴思 | 2019 | China Medical Abstracts(Internal Medicine)2019，36，2： | 0 |
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