Alzheimer Disease: Zhang ZX

Zhang ZX. · Department of Neurology, PUMC Hospital, CAMS and PUMC, Beijing 100730, China. · Zhongguo Yi Xue Ke Xue Yuan Xue Bao. · Pubmed #15244005 No free full text.

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Kalaria RN, Maestre GE, Arizaga R, Friedland RP, Galasko D, Hall K, Luchsinger JA, Ogunniyi A, Perry EK, Potocnik F, Prince M, Stewart R, Wimo A, Zhang ZX, Antuono P, Anonymous00415. · Institute for Ageing and Health, Newcastle General Hospital, Newcastle upon Tyne, UK. · Lancet Neurol. · Pubmed #18667359 No free full text.

Abstract: Despite mortality due to communicable diseases, poverty, and human conflicts, dementia incidence is destined to increase in the developing world in tandem with the ageing population. Current data from developing countries suggest that age-adjusted dementia prevalence estimates in 65 year olds are high (>or=5%) in certain Asian and Latin American countries, but consistently low (1-3%) in India and sub-Saharan Africa; Alzheimer's disease accounts for 60% whereas vascular dementia accounts for approximately 30% of the prevalence. Early-onset familial forms of dementia with single-gene defects occur in Latin America, Asia, and Africa. Illiteracy remains a risk factor for dementia. The APOE epsilon4 allele does not influence dementia progression in sub-Saharan Africans. Vascular factors, such as hypertension and type 2 diabetes, are likely to increase the burden of dementia. Use of traditional diets and medicinal plant extracts might aid prevention and treatment. Dementia costs in developing countries are estimated to be US$73 billion yearly, but care demands social protection, which seems scarce in these regions.

Zhou YT, Zhang ZX, Chan P, He XM, Tang MN, Wu CB, Hong Z. · Department of Neurology and Neurobiology, Key Laboratory of Neurodegenerative Diseases for Ministry of Education, Beijing Institute of Geriatrics and Xuanwu Hospital of Capital University of Medical Sciences, 100053 Beijing, China. · Neurosci Lett. · Pubmed #18706476 No free full text.

Abstract: Alzheimer's disease (AD) is the most common neurodegenerative disorders in the elderly. Low-density lipoprotein receptor-related protein (LRP), as a receptor of apolipoprotein E (APOE), APP, and alpha2 macroglobulin (alpha2-M), keeps the balance between degeneration and production of beta-amyloid protein (Abeta) clearance. Its gene had been defined as a candidate gene for AD, but the results were not universal. Total 496 AD patients and 478 controls were recruited in Chinese Han population and real-time PCR was used to detect the polymorphism of LRP C766T. Multiple logistic regression, Chi-square test and survival analysis were performed to explore the association. The distribution of LRP genotypes and alleles was significantly different between cases and controls, and T allele could reduce the risk for developing AD (OR of CT genotype: 0.57; 95% CI: 0.38-0.85, rho=0.003; OR of T allele: 0.57; 95% CI: 0.39-0.83, rho=0.003). TT genotype carriers had 5 years later for developing AD compared with CC genotype carriers, but survival analysis did not conform this (LRP TT vs. CT and CC log rank chi(2)=2.71, rho=0.26). The distribution of LRP C766T genotypes and alleles was different among different severity stratified by MMSE yet (rho=0.26). Our data suggested that the polymorphism of LRP C766T was strongly associated with AD and T allele might be a protective factor for AD in Chinese Han population.

Zhao HL, Li XQ, Zhang ZX, Bi XH, Wang B, Zhang JW. · National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, PR China. · Brain Res. · Pubmed #18329006 No free full text.

Abstract: Homocysteine has been identified to be associated with Alzheimer disease (AD) and methionine synthase (MS) is one of the enzymes involved in homocysteine metabolism. Confused data were reported on the association between the MS 2756 A>G polymorphism and AD. To determine if this polymorphism could affect the occurrence of AD, we investigated the association between the MS 2756 A>G polymorphism and AD risk in 353 sporadic AD patients and 346 controls in a Chinese Han population. No significant differences of allele and genotype distributions between the AD cases and the controls were observed in the total samples, neither when the samples were stratified by age/age at onset and gender. When the samples were stratified by APOE epsilon4 status, a trend of A allele and AA genotype over-representation in the AD patients in comparison with the controls was observed, but it was not statistically significant (for the alleles, A versus G OR=1.549, 95% CI 0.920-2.609, p=0.098; for the genotypes, AA versus AG+GG OR=1.485, 95% CI 0.861-2.560, p=0.153). Similar trend was observed in the APOE epsilon4 non-carrier samples of the >or=65 year subgroups and it was not statistically significant too (for the alleles, A versus G OR=1.682, 95% CI 0.901-3.140, p=0.099, for the genotypes, AA versus AG+GG OR=1.690, 95% CI 0.884-3.232, p=0.110). Our data did not reveal significant association between the MS 2756 A>G polymorphism and AD development. However, a weak effect of the A allele on developing AD could not be completely excluded.

Bian JT, Zhao HL, Zhang ZX, Bi XH, Zhang JW. · Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, People's Republic of China. · J Mol Neurosci. · Pubmed #18253865 No free full text.

Abstract: Several lines of evidence support a role of oxidative stress in the pathology of Alzheimer's disease (AD). NAD(P)H:quinone oxidoreductase 1 (NQO1) catalyzes the two-electron reduction of quinones, preventing their participation in redox cycling and subsequent generation of reactive oxygen species. We examined association between the NQO1 C609T gene polymorphism and sporadic AD in a Chinese population comprising 311 AD patients and 330 controls. Our results showed a higher T-allele frequency in the AD cases compared with the controls. The difference was close to but did not reach statistically significant level [p = 0.059; odds ratio (OR) T versus C = 1.236; 95% confidence interval (95% CI), 0.992-1.540]. A significantly low C/C genotype frequency in the AD cases compared with the controls was detected (p = 0.025; OR C/C versus C/T + T/T = 0.674; 95% CI, 1.049-2.098) and APOE epsilon4 status analysis revealed significant difference in the APOE epsilon4 non-carriers (p = 0.036; OR = 0.633; 95% CI, 1.027-2.427). In the > or =65 years samples, significantly low C/C frequency in the AD cases in comparison with the controls was observed in the APOE epsilon4 non-carriers (p = 0.045; OR = 0.595; 95% CI, 1.010-2.794). These results indicated that the C/C genotype had a possible protective effect against AD development, and the T allele might be a weak risk factor for late onset AD.

He XM, Zhang ZX, Zhang JW, Zhou YT, Tang MN, Wu CB, Hong Z. · Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. · Neuropsychobiology. · Pubmed #17657167 No free full text.

Abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by excessive neuronal loss in specific regions of the brain. Among the areas most severely affected are the basal forebrain cholinergic neurons and their projection regions, the hippocampus and the cortex. Several lines of evidence have made brain-derived neurotrophic factor (BDNF) an important candidate gene conferring risk for AD. Recently, several reports investigated the association between a single nucleotide polymorphism (Val66Met, rs6265) of the BDNF gene and AD but yielded ambiguous results. To figure out the association of this single nucleotide polymorphism in the BDNF gene with sporadic AD in a Chinese Han population, we analyzed 513 patients with AD and 575 controls for the genetic association studies. Our results indicated that the distribution of the BDNF genotypes and alleles did not differ significantly. Similar results were observed when the AD and control groups were stratified by age/age at onset and sex. Our data also showed that in the Chinese Han population, the frequencies of the BDNF Met allele (46.5%) and Val allele (53.5%) were significantly different from ethnic groups from Italy, Japan and the USA. The present data revealed no significant effect of the genotypes on the age at onset for developing AD, and no significant association between the genotypes and the severity of the disease.

Zhang ZX, Zahner GE, Román GC, Liu XH, Wu CB, Hong Z, Hong X, Tang MN, Zhou B, Qu QM, Zhang XJ, Li H. · Department of Clinical Epidemiology, Peking Union Medical College Hospital, Beijing, PR China. · Neuroepidemiology. · Pubmed #17035714 links to  free full text

Abstract: OBJECTIVE: To characterize sociodemographic variations in the prevalence of AD and VaD in China. METHODS: Data were collected in a 1997-1998, cross-sectional, door-to-door prevalence survey of 34,807 community residents ages > or =55 years in Beijing, Shanghai, Chengdu and Xian. Initial diagnoses of AD and VaD were assessed by clinicians using standardized protocols, according to the NINCDS-ADRDA and NINDS-AIREN criteria; diagnoses were confirmed after 6 months by repeating neuropsychological evaluations. Prevalence odds ratios were estimated in logistic models adjusting for survey design, age, and other sociodemographic factors. RESULTS: We identified 732 prevalent cases of AD and 295 cases of VaD. Adjusting for all sociodemographic factors concurrently, prevalence odds of AD and VaD were higher in northern versus southern China. Age trends for AD appeared different in western and eastern China. AD also showed an age-adjusted elevation among women and, in the fully adjusted model, a gender education interaction indicating a female preponderance in the highest education group. North-south variation for VaD was age-dependent. In the fully adjusted model, for AD, widowed had significantly higher prevalence odds; for VaD, widowed persons and minorities had significantly lower prevalence odds; professionals had statistically significant and borderline lower prevalence odds for both VaD and AD; sales-service occupations had significantly lower odds for AD only. CONCLUSION: We observed variations in prevalence for AD and VaD in different regions and demographic groups in China that persisted after controlling for potential confounding factors. Sociodemographic factors are probable surrogates for conditions such as lifestyle, environment, comorbidities, and life expectancy.

He XM, Zhang ZX, Zhang JW, Zhou YT, Tang MN, Wu CB, Hong Z. · Department of Neurology, Peking Union Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China. · Chin Med J (Engl). · Pubmed #16863614 links to  free full text

Abstract: BACKGROUND: Oxidative stress such as low-density lipoprotein (LDL) oxidation is thought to be an important mechanism in Alzheimer's disease (AD). Paraoxonase 1 (PON1), an enzyme located on high-density lipoprotein, can prevent LDL from oxidation to some extent. It is also a potent cholinesterase inhibitor and an arylesterase, combating organophosphate poisoning and metabolization of environmental neurotoxins which might be responsible for neurodegeneration with aging. We evaluated the association of Gln192Arg polymorphism in the PON1 gene with AD in a Chinese Han ethnic population. METHODS: Patients and age-matched controls were recruited from outpatient clinics and a population-based epidemiological survey, respectively. Gln192Arg polymorphism in the PON1 gene was detected by allele-specific PCR technique in 521 patients with AD and 578 healthy controls. RESULTS: The presence of at least one of PON1 R alleles (Q/R or R/R) was lower in AD patients than in the controls (82.7% vs 87.4%; chi(2) = 4.68, P = 0.03). PON1 gene R allele frequency was lower in AD patients than in the controls (60.7% vs 64.7%; chi(2) = 3.85, P = 0.05). One-way ANOVA showed that PON1 genotype had no effect on the age of onset for developing AD. Logistic regression analysis demonstrated the age and sex-adjusted odds ratio (OR) for the risk of AD in PON1 of PON1 R allele carriers was 0.71 (P = 0.044, 95% CI, 0.51 - 0.99). CONCLUSION: Our results indicate that Gln192Arg polymorphism in the PON1 gene is associated with AD, and PON1 R allele might be a protective factor for AD in a Chinese Han ethnic population.

Hu HT, Zhang ZX, Yao JL, Yu HZ, Wang YH, Tang HC, Ji CJ, Xu T. · Department of Neurology and Clinical Epidemiology Unit, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China. · Zhonghua Nei Ke Za Zhi. · Pubmed #16780671 No free full text.

Abstract: OBJECTIVE: To evaluate the clinical efficacy and safety of akatinol memantine in the treatment of patients with mild to moderate Alzheimer disease (AD). METHODS: One hundred patients with diagnosis of possible or probable AD and Mini Mental State Examination total scores between 10 and 26 from 6 centers in two cities of China were randomly divided into two groups: akatinol memantine group (n = 50, given akatinol memantine 5 mg/d in first week, 10 mg/d in second week, 15 mg/d in third week and 20 mg/d from fourth to sixteenth week); donepezil group (n = 50, donepezil 5 mg/d). Different scales were used to evaluated cognitive function (MMSE), activity of daily life and behavior and mood (Blessed-Roth scale) as well as the severity of dementia (GDS). Safety evaluation was conducted every 4 weeks. RESULTS: In comparison with the baseline data, there were significant improvements in cognition assessed with MMSE on 16th week in akatinol memantine group (P = 0.000) and donepezil group (P = 0.000) respectively; There also were significant improvements in activity of daily life, behavior and mood assessed by Blessed-Roth scale in akatinol memantine group (P = 0.000) and donepezil group (P = 0.000) on 8th week and 16th week. However there was no improvements in the change of the basic habit of life assessed with the Part II of Blessed-Roth scale (P > 0.05), and nor an improvements in the serious level of dementia assessed with GDS (P > 0.05). In comparison with the data in donepezil group, there were no improvement in the change of MMSE score, Blessed-Roth scale score and GDS score in akatinol memantine group on 16th week (P > 0.05). Mild and transient adverse events were observed in 6% of akatinol memantine group. CONCLUSION: As a safe and effective medicine, akatinol memantine, which has a similar effect as donepezil for AD, can remarkably improve the cognition, behavior, and mood of AD patients.

He XM, Zhang ZX, Zhang JW, Zhou YT, Tang MN, Wu CB, Hong Z. · Department of Neurology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China. · Zhonghua Nei Ke Za Zhi. · Pubmed #16780669 No free full text.

Abstract: OBJECTIVE: The aim of this study was to evaluate the association of Gln192Arg polymorphism in paraoxonase 1 (PON1) gene with Alzheimer's disease (AD) in Chinese Han population. METHODS: Gln192Arg polymorphism in PON1 gene was detected with real-time PCR (RT-PCR) technique in 521 patients with AD and 578 healthy controls. RESULTS: The presence of at least one of PON1 R allele (Q/R or R/R) was lower in AD patients as compared with the controls (82.7% vs 87.4%; chi(2) = 4.68, P = 0.03). PON1 gene R allele frequency was lower in AD patients as compared with the controls (60.7% vs 64.7%; chi(2) = 3.85, P = 0.05). One-Way ANOVA showed that PON1 genotype had no effect on the age of onset of AD. Logistic regression analysis demonstrated that the age and sex-adjusted OR for the risk of AD in PON1 R allele carriers was 0.71 (P = 0.044, 95% CI = 0.51 - 0.99). CONCLUSION: Our results indicate that Gln192Arg polymorphism in PON1 gene is associated with AD and PON1 R allele might be a protective factor for AD in Chinese Han population.

Zhou YT, Zhang ZX, Zhang JW, He XM, Xu T. · Department of Neurology, PUMC Hospital, CAMS and PUMC, Beijing 100730, China. · Zhongguo Yi Xue Ke Xue Yuan Xue Bao. · Pubmed #16733901 No free full text.

Abstract: OBJECTIVE: To explore the possible association between interleukin-1 alpha-889C/T (IL-1 alpha-889 C/T) polymorphism and Alzheimer's disease (AD) in Chinese Han population. METHODS: A total of 520 AD patients and 505 normal controls were enrolled. The polymorphism of IL-1 alpha-889C/T was detected with real-time polymerase chain reaction. Multiple logistic regression and chi square test were performed for statistical analysis. RESULTS: The frequencies of C/C, C/T, and T/T genotypes were 70.96%, 25.77%, and 3.27%, respectively, among AD patients, and 80.59%, 18.22%, and 1.19%, respectively, among non-dementia controls. In multivariate analysis, T/T and C/T genotypes of IL-1 alpha-889, age > or =65 years, and female were risk factors for AD. Adjusted for the age and sex, T/T and C/T genotypes were still associated with AD. The odds ratio for AD were 3.57 and 1.74 for individuals with T/T and C/T genotypes compared with individuals with C/C genotype. P value was 0. 019 and 0. 001, respectively. CONCLUSION: The IL-1 alpha-889 T/T and C/T genotypes are likely to be susceptible factors for the development of AD in Chinese Han population. The susceptibility genotype, female, and age > or =65 years are risk factors for AD.

He XM, Zhang ZX, Zhang JW, Zhou YT, Tang MN, Wu CB, Hong Z. · Department of Neurology, Peking Union Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730 Beijing, China. · Brain Res. · Pubmed #16703675 No free full text.

Abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by excessive neuronal loss, intracellular neurofibrillary tangles and extracellular deposition of amyloid beta-peptide (Abeta). The Fas antigen is a cell surface receptor-mediating cell apoptosis. Several lines of evidence have made Fas/Fas ligand induced apoptosis play an important role in the pathogenesis of AD. Moreover, the Fas gene is located on chromosome 10q24.1, a region of linkage to late-onset AD. Several reports have investigated the association between a single nucleotide polymorphism (SNP) that is located at position -670 of Fas gene and AD, but yielded ambiguous results. To figure out the association of this SNP with sporadic AD in Chinese Han population, we have analyzed 509 patients with AD and 561 controls for the genetic association studies. Our results indicate that the distribution of the Fas genotypes (chi(2) = 0.66, P = 0.72) and alleles (chi(2) = 0.70, P = 0.40) did not differ significantly. The similar results were observed when AD and control groups were stratified by age/age at onset and sex (P > 0.10). The present data revealed no significant effect of the genotypes on the age of onset for developing AD, and no significant association between the genotypes and the severity of the disease.

Bian JT, Zhang JW, Zhang ZX, Zhao HL. · National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, PR China. · Neurosci Lett. · Pubmed #16054753 No free full text.

Abstract: A functional polymorphism in the coding region of brain-derived neurotrophic factor (BDNF) gene (196 A/G, Met66Val) has recently been reported to be associated with Alzheimer's disease (AD) and with an overrepresentation of G allele in AD patients, but different results have also been presented. We conducted a case-control study to analyze the association between the BDNF A/G polymorphism and sporadic AD in a sample composed of 203 AD patients and 239 controls from Mainland Chinese Han population. No association between the polymorphism and AD, no association between the polymorphism and age at onset in AD, and no significant interaction between BDNF and apolipoprotein E (APOE) genotype were detected in either the total or the male samples. However, a significantly high frequency of the GG genotype in the female controls compared with the female patients was detected. A postponed age at onset in the female patients with the GG genotype was also observed. These results suggest that the GG genotype has a protection effect from AD development in females. A significant low frequency of AD patients with the BDNF GG genotype in the AD APOEepsilon4 carriers compared with the frequency of the controls with the BDNF GG genotype in the control APOEepsilon4 carriers was also detected in the female individuals, suggesting that the BDNF GG genotype may reduce the effect of APOEepsilon4 on AD risk in females. Additionally, low frequencies of BDNF G allele and GG genotype were revealed in Chinese when compared with that in the other race populations so far reported.

Zhang JW, Li XQ, Zhang ZX, Chen D, Zhao HL, Wu YN, Qu QM. · National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. · Dement Geriatr Cogn Disord. · Pubmed #15832037 No free full text.

Abstract: Angiotensin-converting enzyme has shown altered activity in patients with neurological diseases. An insertion/deletion (I/D) polymorphism of the DCP1 gene encoding angiotensin-converting enzyme has been reported to be associated with the risk for Alzheimer's disease (AD), but ambiguous results have also been presented. We conducted a case-control study in a sample composed of 192 sporadic AD patients and 195 age- and sex-matched controls from Chinese Han population in Beijing and Xi'an districts to investigate the possible effect of the polymorphism. Our data revealed no association between the DCP1 polymorphism and AD risk in the total sample. There was no significant difference in the DCP1 allele or genotype frequencies between cases and controls when stratified by gender and APOE epsilon4 status. However, the D allele and D/D genotype were more frequent among AD patients between 66 and 70 years compared with controls (D allele: OR=2.8, 95% CI=1.5-5.2, p=0.001; D/D genotype: OR=5.9, 95% CI=1.7-19.9, p=0.002). Our results provided new proof that the DCP1 D allele was a probable risk factor for late-onset AD. Its role was independent and was limited to the population at a certain age.

Zhang ZX, Zahner GE, Román GC, Liu J, Hong Z, Qu QM, Liu XH, Zhang XJ, Zhou B, Wu CB, Tang MN, Hong X, Li H. · Department of Clinical Epidemiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China. · Arch Neurol. · Pubmed #15767510 links to  free full text

Abstract: BACKGROUND: Prevalences of Alzheimer disease (AD) and vascular dementia (VaD) in China reportedly differ from those in Western countries. OBJECTIVE: To estimate prevalence of AD and VaD in 4 regions of China. DESIGN: Cross-sectional, population-based prevalence survey with a stratified, multistage cluster sampling design. SETTING: Rural (n = 99) and urbanized (n = 71) communities of Beijing, Xian, Shanghai, and Chengdu. PARTICIPANTS: A sample of 34 807 community residents (94% of those eligible) 55 years or older. MAIN OUTCOME MEASURES: Participants were screened with the Chinese Mini-Mental State Examination. Those who screened positive (n = 3950) underwent a standardized diagnostic workup. Screening sensitivity was assessed in a 3.3% random sample (n = 1008 of the 30 857 who passed the screening). Diagnoses of AD and VaD were made according to National Institute of Neurological and Communicative Diseases and Stroke-Alzheimer Disease and Related Disorders Association and National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences criteria, respectively. Final diagnoses were made after a 6-month confirmation interval. RESULTS: We identified 732 AD cases and 295 VaD cases. Prevalence in persons 65 years or older was 3.5% (95% confidence interval, 3.0%-3.9%) for AD and 1.1% (95% confidence interval, 0.9%-1.1%) for VaD. After post hoc correction for negative screening errors, prevalence increased to 4.8% for AD and remained at 1.1% for VaD. CONCLUSION: Prevalence of dementia subtypes in China is comparable with that in Western countries.

Li XQ, Zhang JW, Zhang ZX, Chen D, Qu QM. · National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Beijing, P.R. China. · J Neural Transm. · Pubmed #15338333 No free full text.

Abstract: Interleukin-1 (IL-1) has been implicated as a key cytokine in Alzheimer's disease (AD) pathogenesis. IL-1 gene polymorphisms, especially IL-1A C((-)889)T polymorphism, have been suggested to be associated with AD risk and onset age. To determine if IL-1 polymorphisms are genetic risk factors for developing AD in Chinese Mainland population, we analyzed IL-1A ((-)889), IL-1B ((-)511) and IL-1RN variable number of tandem repeat (VNTR) polymorphisms in a sample of 145 sporadic AD patients and 181 healthy controls. Our data revealed that the three polymorphisms in IL-1 gene cluster might not play a key role in AD pathogenesis in Chinese Mainland Han population.

Li XQ, Chen D, Zhang ZX, Qu QM, Zhang JW. · National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Peking Union Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China. · Dement Geriatr Cogn Disord. · Pubmed #15211064 No free full text.

Abstract: Cathepsin D (CTSD) is an intracellular aspartyl protease, which is active in the endosomal/lysosomal system. CTSD may play a role in Alzheimer's disease (AD) through cleaving the amyloid precursor protein into beta-amyloid peptide and degrading tau protein into fragments. A functional polymorphism in exon 2 of the cathepsin D gene (C-->T, Ala224Val) has recently been reported to increase the risk for AD in some of the Caucasian populations, with a significant overrepresentation of the T allele, but these reports have not been universally duplicated. We performed an association study between CTSD polymorphism and AD in 156 sporadic AD patients and 183 controls of Chinese Han ethnicity. Our data revealed that the distribution of CTSD genotypes and alleles was similar in patients and controls. No direct association was found between CTSD polymorphism and AD risk. There might be a weak synergistic interaction between CTSD T and APOEepsilon4 allele in increasing the risk for developing AD.

Sun Y, Du XK, Zhang ZX, Chen X. · Department of Radiology, People's Hospital, Peking University, Beijing 100044, China. · Zhongguo Yi Xue Ke Xue Yuan Xue Bao. · Pubmed #15171548 No free full text.

Abstract: OBJECTIVE: To determine the relationship between the extent of the damage and clinical data in Alzheimer's disease (AD). METHODS: Twenty-two patients with AD and twenty-two controls received MR-diffusion tensor scanning. The fractional anisotropy (FA) values of white matter in AD patients were measured respectively in parietal lobe and the genu of corpus callosum. Independent-samples t-test for non-paired data was used to test differences between AD and controls for FA values. Correlation analysis was applied to reveal the correlations between FA values in each region and the MMSE, FOM, RVR, BD and DS scores. RESULTS: Positive correlations were found between FA values in left parietal lobe and FOM/DS, and between FA values in genu of corpus callosum and MMSE scores. CONCLUSIONS: In AD, the MR-DTI can reflect the relationship between the degree of white matter abnormalities and the cognitive impairment.

Wei J, Hong X, Wu LY, Ni J, Cao YZ, Chen X, Zhang ZX. · Department of Neurology, PUMC Hospital, CAMS and PUMC, Beijing 100730, China. · Zhongguo Yi Xue Ke Xue Yuan Xue Bao. · Pubmed #15171547 No free full text.

Abstract: OBJECTIVE: To evaluate distribution and influence factors of logic memory (LM) modified in assessing and scoring method in normal population and Alzheimer's disease (AD) patients, and definite the cut-off point of the modified scale. METHODS: Totally 183 AD patients, including 118 mild and 65 moderate in degree, 1,417 controls, including 1,283 normal individuals and 134 individuals suffered from other diseases, were recruited in this study. Modified LM was conducted. RESULTS: Educational level (F=354.36, STB=0.46, P=0.0001) was the most obvious factor in demographic data to influence total score in normal control group by a fitting of multiple regression models. The total score increased with the rising of educational level in normal controls (P=0.0001) and other diseases controls (P=0.0001), but not in AD cases (P=0.1365). The total scores were significantly different among normal controls (20.2 +/- 0.2), other diseases controls (17.5 +/- 0.5), mild AD patients (9.6 +/- 0.5) and moderate AD patients (7.1 +/- 0.7) (P=0.0001, P=0.0059), after adjusted educational level, age, sex and rural/urban status by multiple analysis covariance. The sensitivity of cut-off points using modified methods to diagnose AD reasonably increased to 71.98%, while the specificity was 94.11%. According to the sum of long-delayed recall and long-delayed recognition, the sensitivity increased with the rising of educational levels. For education levels at illiteracy, elementary school, junior middle school, senior middle school and above senior middle school, the cut-off points for total score of modified method were 6.5, 9.5, 10.8, 13 and 15.8, respectively, and for sum of long-delayed recall and long-delayed recognition the cut-off points were 5, 6, 8, 9, 10. CONCLUSIONS: When modified LM used as a neuropsychological assessment, it is with high specificity, high accuracy and reasonable sensitivity. It is suitable for the diagnosis of AD in early stages, especially for individuals with high educational levels.

Chen X, Zhang ZX, Huang JB, Wen HB. · Department of Clinical Neurology, PUMC Hospital, CAMS and PUMC, Beijing 100730, China. · Zhongguo Yi Xue Ke Xue Yuan Xue Bao. · Pubmed #15171546 No free full text.

Abstract: OBJECTIVE: To investigate the clinical features of Alzheimer's disease (AD) and vascular dementia (VaD), and to find effective methods for differential diagnosis between the two entities. METHODS: Totally 112 AD patients and 92 VaD patients were enrolled in this study, consisted of patients from the memory clinics and patients from the community population visited during the epidemiological survey from 1996 to 2000. Diagnosis of dementia, probable AD and probable VaD were made according to international criteria. Results of specific neuroimaging examination were referred to verify the diagnosis and the final diagnosis of each patient was determined from the discussion between clinical experts and radiological professionals. Analysis on clinical and neuroimaging data was performed, aiming at finding differential points between the two dementia-subtypes. A logistic binary multiple regression analysis was performed to pick out those statistically significant clinical features for differential diagnosis at last. RESULTS: AD and VaD patients have different clinical features in various demented stages, therefore the indexes that differentiate the two dementia subtypes change accordingly. The predominant features of mild AD appear to be deficits of prolonged memory and learning ability, while the major impairment of mild VaD patients is decline of calculating ability. With the progress of dementia, learning ability and attention turn to be the effective indexes for differential diagnosis. In the mild and moderate demented stage, AD patients are inferior to VaD patients in handling finacial affairs and making phone calls, while VaD patients often degenerate in daily activities concerning with both physical ability and intellectual level. Severe VaD patients appears more global degeneration of living ability compared to AD patients. The difference of ADL scores between the two subtypes is significant in moderate to severe demented patients (P < 0.05). Psychological behavior symptoms, such as repeatedly collecting useless things, are the characteristic manifestation to differentiate AD from VaD in all clinical stages. CONCLUSIONS: The results of our study indicate that substantial differences exist between AD and VaD patients. Such differences can be attributed to the differences of lesion nature and distribution, as well as the underlying pathophysiological procedures of each disease.

Wang QH, Zhang JW, Zhang ZX, Wu CB, Chen D. · Department of Neurology, PUMC Hospital, CAMS and PUMC, Beijing 100730, China. · Zhongguo Yi Xue Ke Xue Yuan Xue Bao. · Pubmed #15171544 No free full text.

Abstract: OBJECTIVE: To explore the association between Alzheimer's disease (AD) and nitric oxide synthase (NOS) III in Chinese Han population. METHODS: Seventy-five AD and 68 normal controls were genotyped for NOS III G894T polymorphism. Genotyping was carried out by PCR-RFLP methods. RESULTS: There were two genotypes of NOS III, GG and GT, in either AD patients or normal controls. The frequencies of these two genotypes were 78.7% and 21.3% in AD patients and 82.4% and 17.6% in normal controls, respectively. No association was found between AD and NOS III genotype (P > 0.05). There were two alleles, G and T, in AD patients and normal controls. The frequencies of these two alleles were 89.3% and 10.7% in AD patients and 91.2% and 8.8% in normal controls, respectively, indicating that there was no association between AD and NOS III allels (P > 0.05). CONCLUSIONS: There was no association between AD and NOS III G894T polymorphism in Chinese Han population.

Tang MN, Zhang ZX, Han HY, Liu XH, Shen Y. · Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730 PR China. · Zhonghua Yi Xue Yi Chuan Xue Za Zhi. · Pubmed #15079806 No free full text.

Abstract: OBJECTIVE: To investigate the correlation between the polymorphisms of apolipoprotein E(APOE), the interleukin-1 alpha (IL-1 alpha ) genes and the susceptibility to Alzheimer's disease(AD). METHODS: Association study was performed in 114 AD patients and 113 healthy elderly individuals from Chengdu, China. Polymorphisms of APOE and IL-1 alpha genes were analyzed with polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The frequency of APOE-epsilon 4-carrying genotype in moderate to severe AD patients (28.6%) was higher than that of mild patients (18.5%) and the controls (14.2%), and the difference between moderate to severe AD group and the control group was significant (OR=2.4, 95%CI: 1.1-5.5). The frequency of epsilon 4 was also of significant difference between the group of moderate to severe dementia and the control group (OR=2.6, 95%CI: 1.3-5.3). However, no significant difference in distribution of IL-1 alpha polymorphism between AD patients and controls was observed. CONCLUSION: The APOE epsilon 4 allele was associated with moderate to severe AD while no association between the IL-1 alpha gene polymorphism and AD was found.

Chen D, Zhang JW, Zhang ZX, Zhao HL, Li XQ, Wu YN, Qu QM. · National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, CAMS & PUMC, Beijing 100005, China. · Yi Chuan Xue Bao. · Pubmed #14986436 No free full text.

Abstract: PCR-RFLP was used to investigate the distribution differences of apolipoprotein E (APOE) alleles and genotypes between sporadic Alzheimer disease (AD) patients (n = 160) and healthy control individuals (n = 195) in Chinese Han population. The results showed that the allelic frequencies of APOE epsilon 2, epsilon 3 and epsilon 4 were 0.056, 0.713 and 0.231 in AD group respectively, and 0.082, 0.844 and 0.074 in control group respectively. The frequency of epsilon 4 allele was significantly higher in AD cases than in control subjects and epsilon 4 allele was associated with AD by an odds ratio (OR) of 3.82 (chi 2 = 28.70, P < 0.001). The probability for APOE epsilon 4-carriers to suffer from AD after 65 years old was 5.38 times of that for APOE epsilon 4 non-carriers (chi 2 = 29.76, P < 0.001), suggesting that age might affect the interaction between APOE epsilon 4 and AD. In addition, our results showed that the distributions of APOE alleles and genotypes were comparable among mild, moderate and severe dementia patients (P > 0.05), suggesting that APOE gene polymorphism was not likely to contribute to dementia severity of AD patients. The frequency of APOE epsilon 4 genotype in female patients was higher than that in male patients(43.0% vs. 36.5%) and females carrying APOE epsilon 4 allele had higher OR value than corresponding males (4.3 vs. 3.3), but the differences were not statistically significant (P > 0.05). As to epsilon 2 allele, its frequency was significantly lower in male subgroup than in female subgroup of AD patients and also than in male subgroup of normal control (P < 0.05), suggesting that epsilon 2 allele was possibly an AD protective factor in Chinese male population.

Chen D, Zhang JW, Zhang ZX, Wu YN, Qu QM. · National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, The Chinese Academy of Medical Sciences and The Peking Union Medical College, Beijing 100005, People's Republic of China. · J Neurol Sci. · Pubmed #14675603 No free full text.

Abstract: This study used case-control method to investigate roles of two alpha 2-macroglobulin (A2M) polymorphisms, a 5-bp insertion/deletion (A2M-I/D) and an A-->G substitution (A2M-A/G), in the development of sporadic Alzheimer disease (AD) in Mainland Han Chinese. Our results showed a trend of lower D-carrying genotype frequency in APOE-epsilon 4 carrying AD patients than in corresponding control subjects (chi(2)=3.67, p=0.055). The ID/AA genotype frequency was lower in AD patients comparing with controls (chi(2)=4.04, p=0.044). In AD patients, the G-carrying genotype frequency was significantly higher in APOE-epsilon 4 carrier subgroup than in APOE-epsilon 4 non-carriers (chi(2)=7.38, OR=2.99, 95% CI: 1.33-6.71, p=0.007). These results indicated that A2M-D allele was probably a weak AD protective factor, and there was a possible interaction of APOE-epsilon 4 and A2M-G alleles to increase AD risk in Mainland Han Chinese.

Wu YN, Zhang JW, Zhang ZX, Qu QM, Chen D. · National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, CAMS, PUMC, Beijing 100005, China. · Zhongguo Yi Xue Ke Xue Yuan Xue Bao. · Pubmed #12905860 No free full text.

Abstract: OBJECTIVE: To analyse the association of apolipoprotein E genotypes with Alzheimer's disease in Chinese population. METHODS: Using PCR and restriction enzyme digestion, we have analyzed ApoE allele frequency of Alzheimer's disease (AD) patients and healthy controls. RESULTS: Among the 56 cases of AD, the frequency of ApoE epsilon 2, ApoE epsilon 3, ApoE epsilon 4 are 3 (2.7%), 84 (75.0%), 25 (22.3%) respectively, while in the 67 controls they are 9 (6.7%), 115 (85.8%), 10 (7.5%) respectively. The frequencies of the two groups have significant difference (P < 0.01) and the frequency of ApoE epsilon 4 allele is higher in AD than that in the health controls and the statistical treatment suggest that there is significant difference (chi 2 = 10.99, P < 0.01, OR = 3.59, 95% CI = 1.54-8.41). The frequency of the ApoE epsilon 3 is lower in AD than that in the health controls and the difference is also statistically significant(P < 0.05). CONCLUSIONS: Our results are consistent with previous work in that proving the ApoE epsilon 4 allele is one of the risk factors of AD. The results also provide a support for the protection effect of ApoE epsilon 3 allele in developing AD.