Objective To generate eukaryotic expression vector of pcDNA3.1-β-site amyloid precursor protein cleaving enzyme (BACE) and obtain its transient expression in COS-7 cells. Methods A 1.5 kb cDNA fragment was amplified from the total RNA of the human neuroblastoma cells by the RT-PCR method and was cloned into the plasmid pcDNA3.1. The vector was identified by the double digestion with restriction enzymes BamHI and XhoI and was sequenced by the Sanger-dideoxy-mediated chain termination. The expression of the BACE gene was detected by immunocytochemistry. Results The results showed that the cDNA fragment included 1.5 kb total coding region. The recombinant eukaryotic cell expression vector of pcDNA3.1-BACE was constructed successfully, and the sequence of insert was identical to the published sequence. The COS-7 cells transfected with the pcDNA3.1BACE plasmid expressed a high level of the BACE protein in the cytoplasm. Conclusion The recombinant plasmid pcDNA3.1-BACE can provide a very useful tool for the research on the cause of Alzheimer’s disease and lay an important foundation for preventing Alzheimer’s disease.
Objective To investigate the memory amelioration of the Alzheimer disease (AD)model rat after being transplanted the single neural stem cells(NSC) and NSC modified with human brain-derived neurotrophic factor（hBDNF） gene. Methods Forty SD rats were divided evenly into 4 groups randomly. The AD model rats were made by cutting unilaterallythe fibria fornix of male rats. Ten to twelve days after surgery, the genetically modified and unmodified NSC were implanted into the lateral cerebral ventricle of group Ⅲ and group Ⅳ respectively. Two weeks after transplantation, theamelioration of memory impairment of the rats was detected by Morris water maze. Results The average escaping latency of the group Ⅲ and group Ⅳ (41.84±21.76 s,25.23±17.06 s respectively) was shorter than that of the group Ⅱ(70.91±23.67 s) (Plt;0.01). The percentage of swimming distance inthe platform quadrant in group Ⅲ (36.9%) and in group Ⅳ(42.0%) was higherthan that in the group Ⅱ(26.0%) (Plt;0.01). More marginal and random strategies were used in group Ⅱ.The percentage of swimming distance in the platform quadrant in group Ⅳ was also greater than that in group Ⅲ(Plt;0.05). There were no significant differences in the average escaping latency, the percentage of swimming distance in the platform quadrant and the probe strategy between group Ⅳ and group Ⅰ(Pgt;0.05).More lineal and oriented strategies were used in group Ⅳ. Conclusion The behavioral amelioration of AD model rat was obtained by transplanting single NSC and hBDNF-gene-modified NSC. The effect of the NSC group modified with hBDNF gene is better than that of the groupⅢ.
Objective To evaluate the efficacy and safety of memantine in the treatment of Alzheimer’s disease (AD). Methods The randomized controlled trials (RCTs) about memantine vs. donepezil for patients with AD from January 1989 to July 2011 were searched in CBM, CNKI, WanFang Data, MEDLINE, OVID, EMbase and The Cochrane Library. Two reviewers independently screened the literatures, extracted the data, and evaluated the methodological quality. Then meta-analyses were conducted by using RevMan 5.0 software. Results The total 12 RCTs were included. Among the 2 716 patients involved, 1 459 were in the memantine group, while the other 1 302 were in the donepezil group. The results of meta-analyses showed that the efficacy of the memantine group was superior to that of the donepezil group in MMSE (MD=0.53, 95%CI 0.21 to 0.85, P=0.001), CIBIC-Plus (MD= –0.19, 95%CI –0.31 to –0.07, P=0.002), NPI (MD= –2.9, 95%CI –4.57 to –1.22, P=0.000 7) and SIB (MD=3.12, 95%CI 0.57 to 5.67, P=0.02), with significant differences; but the efficacy of the two groups was similar in ADCS-ADL19 (MD=0.29, 95%CI –0.03 to 0.60, P=0.07). There was no significant difference between the two groups in incidence of side effects (RR=1.14, 95%CI 0.94 to 1.38, P=0.17), but the tolerability of the memantine group was much better (RR=0.78, 95%CI 0.63 to 0.97, P=0.03). Conclusion Based on the current studies, memantine is superior to donepezil in treating Alzheimer’s disease (AD) at present. Although the side effects are similar to donepezil, memantine has much better intolerability and is considered to be safe and effective. For the quality restrictions and possible publication bias of the included studies, more double blind RCTs with high quality are required to further assess the effects.
Objective To evaluate the relationship between genetic polymorphism of ApoE and Alzheimer’s disease in Chinese population. Methods Such databases as PubMed, EBSCO, CNKI, CBM, and WangFang Data were searched from their establishment to December 2010 to collect the literature about the relationship between genetic polymorphism of ApoE and Alzheimer’s disease in Chinese population. RevMan 5.0 was adopted to conduct consistency check and data merging, and to evaluate publication bias. Results ApoEε4 was the risky allele (Plt;0.05) in Chinese population, and its pooled odds ratios and 95%CI was 3.53 (2.49 to 5.00). ApoEε3 was the protective alleles (Plt;0.05) in Chinese population, and its pooled odds ratios and 95%CI was 0.52 (0.40 to 0.68). ApoEε4/ε4, ApoEε4/ε3, and ApoEε4/ε2 were the risky genotypes (all Plt;0.05) in Chinese population, and their pooled odds ratios and 95%CI were 10.17 (4.25 to 24.19), 2.57 (2.04 to 3.25), and 1.94 (1.13 to 3.34), respectively. ApoEε3/ε3 was the protective genotype (Plt;0.05) in Chinese population, and its pooled odds ratios and 95%CI was 0.67 (0.57 to 0.77). Conclusion In Chinese population, some ApoE alleles and genotypes are associated with Alzheimer’s disease.
【摘要】 目的 探讨3分法画钟测验（clock drawing test，CDT）对阿尔茨海默病患者（Alzheimer disease，AD）与血管性痴呆患者（vascular dementia，VD）的鉴别作用。 方法 收集四川大学华西医院神经内科门诊及住院部2009年9月-2010年6月就诊的认知功能障碍患者150例，进行病史采集及神经心理测试量表，筛选出AD患者57例及VD患者43例，共计纳入100例。在两者间进行CDT，分析两者间CDT有无差别、CDT与中文版简易智能量表（Chinese version of the mini-mental state examination，MMSE）及临床痴呆评定量表（clinical dementia rating scale，CDR）的相关性。 结果 AD患者及VD患者间CDT差异无统计学意义（Pgt;0.05）；CDT与MMSE及CDR有相关性，Spearman相关系数分别为0.573和-0.542（Plt;0.001）。 结论 3分法画钟测验无法准确区分AD和VD，但对粗略判断AD及VD程度可能有一定效果。【Abstract】 Objective To investigate the differential function of the three-point scoring system for the clock drawing test (CDT) between Alzheimer’s disease (AD) and vascular dementia (VD). Methods We analyzed the clinical data of 150 patients with cognitive impairment treated in the neurology and inpatient departments of our hospital from September 2009 to July 2010. Medical history of the subjects were collected. Through the assessment by neurological and psychological rating scale, we picked out 57 patients with AD and 43 with VD and tested them with CDT. The difference of CDT results between the two groups, and the correlation of CDT with Chinese version of the mini-mental state examination (MMSE) and clinical dementia rating scale (CDR) were analyzed. Results There was no statistical difference of CDT results between AD and VD patients (Pgt;0.005). CDT had a correlations with MMSE and CDR, the Spearman correlation coefficient being 0.573 and -0.542 respectively (Plt;0.001). Conclusion The three-point scoring system for the clock drawing test cannot differentiate exactly between Alzheimer Disease and Vascular Dementia, but it can make a gross judgment of the degree of AD and VD.
ObjectiveTo investigate the quality of life of family caregivers of patients with Alzheimer's disease (AD) and to explore the related factors. MethodsTwenty family caregivers of patients with Alzheimer's disease were surveyed with short form 36 health survey questionnaire between October 2013 and August 2014. ResultsThe subjects who were over 60 years old had lower scores in the dimensions of physical functioning, role limitations due to physical problem and role limitations due to emotional problem than those below 60 years old. Female subjects scored better than male subjects in the dimension of vitality. The sons and daughters had higher scores than the wives and husbands in the dimensions of physical functioning, role limitations due to physical problem and role limitations due to emotional problem. The subjects whose patients had medical insurance scored better than those whose patients with no insurance. The differences above were all statistically significant. The scores of caregivers with senior middle school edudation or above were higher than the caregivers with lower education level in the dimensions of mental health, vitality and general health perceptions. ConclusionThe quality of life of the family members of AD patients is obviously affected by many factors. It is very important to implement planned, targeted, reasonable and effective interventions to enhance the quality of life of these people.
Wavelet entropy is a quantitative index to describe the complexity of signals. Continuous wavelet transform method was employed to analyze the spontaneous electroencephalogram (EEG) signals of mild, moderate and severe Alzheimer's disease (AD) patients and normal elderly control people in this study. Wavelet power spectrums of EEG signals were calculated based on wavelet coefficients. Wavelet entropies of mild, moderate and severe AD patients were compared with those of normal controls. The correlation analysis between wavelet entropy and MMSE score was carried out. There existed significant difference on wavelet entropy among mild, moderate, severe AD patients and normal controls (P<0.01). Group comparisons showed that wavelet entropy for mild, moderate, severe AD patients was significantly lower than that for normal controls, which was related to the narrow distribution of their wavelet power spectrums. The statistical difference was significant (P<0.05). Further studies showed that the wavelet entropy of EEG and the MMSE score were significantly correlated (r=0.601-0.799, P<0.01). Wavelet entropy is a quantitative indicator describing the complexity of EEG signals. Wavelet entropy is likely to be an electrophysiological index for AD diagnosis and severity assessment.
It is generally considered that various regulatory activities between genes are contained in the gene expression datasets. Therefore, the underlying gene regulatory relationship and the biologically useful information can be found by modeling the gene regulatory network from the gene expression data. In our study, two unsupervised matrix factorization methods, independent component analysis (ICA) and nonnegative matrix factorization (NMF), were proposed to identify significant genes and model the regulatory network using the microarray gene expression data of Alzheimer's disease (AD). By bio-molecular analyzing of the pathways, the differences between ICA and NMF have been explored and the fact, which the inflammatory reaction is one of the main pathological mechanisms of AD, is also emphasized. It was demonstrated that our study gave a novel and valuable method for the research of early detection and pathological mechanism, biomarkers' findings of AD.