Yu-Lei Deng

Plasma metabolite profiles of Alzheimer's disease and mild cognitive impairment.

Previous studies have demonstrated altered metabolites in samples of Alzheimers disease (AD) patients. However, the sample size from many of them is relatively small and the metabolites are relatively limited. Here we applied a comprehensive platform using ultraperformance liquid chromatography-time-of-flight mass spectrometry and gas chromatography-time-of-flight mass spectrometry to analyze plasma samples from AD patients, amnestic mild cognitive impairment (aMCI) patients, and normal controls. A biomarker panel consisting of six plasma metabolites (arachidonic acid, N,N-dimethylglycine, thymine, glutamine, glutamic acid, and cytidine) was identified to discriminate AD patients from normal control. Another panel of five plasma metabolites (thymine, arachidonic acid, 2-aminoadipic acid, N,N-dimethylglycine, and 5,8-tetradecadienoic acid) was able to differentiate aMCI patients from control subjects. Both biomarker panels had good agreements with clinical diagnosis. The 2 panels of metabolite markers were all involved in fatty acid metabolism, one-carbon metabolism, amino acid metabolism, and nucleic acid metabolism. Additionally, no altered metabolites were found among the patients at different stages, as well as among those on anticholinesterase medication and those without anticholinesterase medication. These findings provide a comprehensive global plasma metabolite profiling and may contribute to making early diagnosis as well as understanding the pathogenic mechanism of AD and aMCI.

Economic Impact of Dementia in Developing Countries: An Evaluation of Alzheimer-Type Dementia in Shanghai, China

The main objective of this study was to assess the economic cost of Alzheimers disease (AD) in Shanghai, China, as a pilot study for future evaluations. Sixty-seven patients with AD were interviewed, and the information of the AD-related cost and resources used was collected from October 2005 to September 2006. By retrospective analysis, annual costs were calculated and expressed in Chinese renminbi (RMB). Direct cost per patient per year averaged approximately 8,432 RMB (1,058 USD), indirect cost per patient per year was 10,568 RMB (1,326 USD), and annual costs were 19,001 RMB (2,384 USD) per patient per year in this investigation. Total cost was significantly associated with the degree of severity including cognitive function (MMSE) and activity of daily living (ADL). With the increase in the number of persons at risk for developing AD, the economic burden of AD patients in China is significantly heavy.

Association Study of Clusterin Polymorphism rs11136000 With Late Onset Alzheimer’s Disease in Chinese Han Population

Objective: We conducted a case–control study to investigate whether clusterin polymorphism (rs11136000) was associated with late-onset Alzheimer’s disease in Chinese Han population. Methods: Polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) assay was performed on genotype rs11136000 and APOEε4 in 127 patients with late-onset Alzheimer’s disease and 143 control individuals. Previous published data from other Chinese samples was also included for further meta-analysis. Results: APOEε4 was demonstrated to increase the risk of Alzheimer’s disease in Chinese population (odds ratio = 2.35, 95% confidence interval: 1.40-3.96). There is no significant association between clusterin rs11136000 with late-onset sporadic AD in our small cohort. However, meta-analysis revealed significant allele and genotype differences between Alzheimer’s disease and controls following a recessive model. Conclusion: Clusterin (rs11136000) was associated with Alzheimer’s disease in Chinese Han population.

CALHM1 P86L Polymorphism is a Risk Factor for Alzheimer's Disease in the Chinese Population

We conducted a case-control study to determine the prevalence of the CALHM1 P86L polymorphism (rs2986017) in patients with Alzheimers disease (AD) in the Chinese population of mainland China, and also to clarify whether this polymorphism is a risk factor for AD. Fourteen heterozygous P86L carriers were identified among 198 AD patients. One control subject was also found to be a P86L heterozygous carrier. The allelic frequencies of the AD patients and control subjects were found to be significantly different. Our study indicates that the CALHM1-P86L polymorphism is associated with AD in the ethnic Chinese Han.

The metric properties of Zarit caregiver burden scale: validation study of a Chinese version.

PurposeTo evaluate the Chinese version of the Zarit Burden Interview (ZBI) as an instrument for measuring strain in Chinese caregivers of elderly people with dementia. Design and MethodsThe objective of the present study was to carry out a metric analysis of a Chinese version of ZBI using a cross-sectional study. Patients and their caregivers completed a variety of questionnaires, including the Mini-Mental State Examination (MMSE), the Neuropsychiatric Inventory (NPI), the Geriatric Depression Scale (GDS), and the Hamilton Anxiety Scale (HAMA). Cronbach α coefficient was used to assess inter-item consistency, and a split half correlation coefficient was used to determine the internal consistency of the ZBI. Correlations between the ZBI and GDS, and the ZBI and HAMA were assessed for convergent validity. Correlations of the ZBI and MMSE, the ZBI and NPI were also calculated to evaluate the possible correlation of caregiver burden with the severity of cognitive impairment and neuropsychiatric symptoms. ResultsThere were 42 patients with dementia in the study. The intraclass correlation coefficient was 0.89 and the split half correlation coefficient was 0.87. The mean ZBI score was 24.40±14.68. Item-total (corrected) correlation showed significant coefficients (rs>0.33, P<0.05) for most items. There was a significant correlation between the ZBI and GDS (rs=0.57, P<0.001), and between the ZBI and HAMA (rs=0.44, P=0.003). Furthermore, there was a significant positive correlation between the ZBI and NPI, the ZBI and the agitation score, the ZBI and the apathy score, and the ZBI and MMSE. ConclusionsThe Chinese version of ZBI meets some of the basic reliability and validity standards required for health status measures. Further studies could lead to a better understanding of the difficulties experienced by caregivers of patients suffering from dementia in China.

Association study of TREM2 polymorphism rs75932628 with late-onset Alzheimer’s disease in Chinese Han population

Abstract Objective: We conducted a case–control study to investigate whether TREM2 polymorphism (rs75932628-T) was associated with late onset Alzheimer’s disease in Chinese Southern Han population. Methods: PCR-restriction fragment length polymorphism assay was performed to genotype rs75932628 in 279 cases with late onset Alzheimer’s diseases patients and 346 control subjects in Shanghai and Nanjing. Results: There was no rs75932628-T variant detected in our sample. However, APOEϵ4 was shown closely associated with the risk of Alzheimer’s disease (Chi-square = 60·288, P = 0·000). Conclusion: Our study suggested that TREM2 (rs75932628-T) was rare in Chinese Han population. Further association studies with large samples are needed to further study the association of TREM2 with late-onset Alzheimer’s disease.

Genetic Polymorphisms in Sigma-1 Receptor and Apolipoprotein E Interact to Influence the Severity of Alzheimers Disease

Apolipoprotein E (APOE) ε4 allele and sigma-1 receptor (SIGMAR1) c.5C (Q2P) polymorphisms have been acknowledged as risk factors for developing Alzheimers disease (AD). However, whether these polymorphisms influence the disease process is unclear. Therefore, two cohorts with a clinical diagnosis of AD were recruited, a postmortem confirmed Australian cohort (82 cases) from the Australian Brain Bank Network, and a Chinese cohort with detailed clinical assessments recruited through an epidemiology study in Shanghai and through the neurology department outpatients clinic of Shanghai Ruijin Hospital (330 cases). SIGMAR1 Q2P and APOE genotyping was performed on all cases. Dementia severity in the Chinese cohort was assessed using MMSE scores, and the stages of senile plaques and neurofibrillary tangles (NFT) assessed in the Australian cohort. Associations between SIGMAR1 Q2P and APOE genotypes and disease severity were assessed using SPSS. Results confirmed that APOE 4 allele associated with increased NFT stages and cognitive decline, with carriers with one APOE ε2 or ε3 allele often having better clinical outcomes compared to carriers with none or two ε2 or ε3 alleles respectively. SIGMAR1 c.5C polymorphism alone did not associate with MMSE score variability in Chinese or with pathological stages in Caucasians. However, the association studies revealed a significant genetic interaction between the APOE ε4 allele and SIGMAR1 2P carriers in both populations, i.e., in APOE non ε4 allele carriers, SIGMAR1 2P variant had increased cognitive dysfunction and more advanced stages of NFT. Our data demonstrate that SIGMAR1 and APOE interact to influence AD severity across ethnic populations.

Validation of the Chinese Version of Addenbrooke's Cognitive Examination-Revised for Screening Mild Alzheimer's Disease and Mild Cognitive Impairment

Background/Aims: As a suitable test to screen for Alzheimers disease (AD) or mild cognitive impairment (MCI), studies to validate the Chinese version of Addenbrookes Cognitive Examination-Revised (ACE-R) are rare. Methods: A total of 151 subjects were recruited and the neuropsychological assessments were employed. One-way analysis of variance and Bonferroni correction were used to compare scores of different psychometric scales. Intraclass correlation coefficient (ICC) and Cronbachs coefficient α were used to evaluate the reliability of psychometric scales. The validity of ACE-R to screen for mild AD and amnestic subtype of MCI (a-MCI) was assessed by receiver operating characteristic (ROC) curves. Results: The Chinese ACE-R had good reliability (inter-rater ICC = 0.994; test-retest ICC = 0.967) as well as reliable internal consistency (Cronbachs coefficient α = 0.859). With its cutoff of 67/68, the sensitivity (0.920) and specificity (0.857) were lower than for the Mini-Mental State Examination (MMSE) cutoff (sensitivity 1.000 and specificity 0.937) to screen for mild AD. However, the sensitivity of ACE-R to screen for a-MCI was superior to the MMSE with a cutoff of 85/86. The specificity of ACE-R was lower than that of the MMSE to screen for a-MCI. The area under the ROC curve of ACE-R was much larger than that of the MMSE (0.836 and 0.751) for detecting a-MCI rather than mild AD. Conclusion: The Chinese ACE-R is a reliable assessment tool for cognitive impairment. It is more sensitive and accurate in screening for a-MCI rather than for AD compared to the MMSE.

A single nucleotide polymorphism in LRP2 is associated with susceptibility to Alzheimer's disease in the Chinese population

BACKGROUND LRP2 (also called megalin) plays a potential key role in the pathogenesis of Alzheimers disease (AD). Recently, one genome-wide association study has revealed that the rs3755166 (G/A) polymorphism located in the LRP2 promoter is associated with development of AD in Caucasians, while there are no studies on the association LRP2 of with AD risk in Asians. METHODS To evaluate the relationship between the rs3755166 polymorphism of the LRP2 gene and AD in the ethnic Chinese Han, we conducted a case-control study (n=361, age>50) to determine the prevalence of one common single-nucleotide polymorphism (SNP) of LRP2 (rs3755166) in patients with AD in Chinese population of Mainland China, and clarified whether this polymorphism is a risk factor for AD. RESULTS The prevalence of the minor allele (A) in the rs3755166 polymorphism was significantly different in AD patients and control subjects (P<0.05). The rs3755166 polymorphism was associated with AD in the ethnic Chinese Han (OR=1.378, 95% CI: 1.017-1.867, P=0.039), and the results were not influenced by age, gender, or APOE status (P=0.441, P=0.94, P=0.432, respectively). CONCLUSION Our data revealed the allele (A) of the rs3755166 polymorphism within LRP2 gene may contribute to AD risk in the Chinese Han Population.

The Genetic Variation of SORCS1 Is Associated with Late-Onset Alzheimer’s Disease in Chinese Han Population

The variations of SORCS1 gene may play potential key roles in late-onset Alzheimer’s disease (LOAD). To evaluate the relationship between the polymorphism of SORCS1 gene and LOAD in the ethnic Han Chinese, we conducted a case–control study to investigate the association between the single-nucleotide polymorphisms (SNPs) in intron 1 of SORCS1 and LOAD in Chinese Han population. Six reported SNPs in intron 1 of SORCS1 were analyzed by Snapshot, genotyping and haplotyping in 236 Chinese LOAD cases and 233 matched controls. The significant differences in frequencies of two SNPs (rs10884402, rs950809) were found between the two groups. In addition, haplotype analyses revealed that, in the LOAD group, the frequency of haplotypes C-C-G-T-C (alleles in order of rs17277986, rs6584777, rs10884402, rs7078098, rs950809 polymorphisms) were significantly higher (Psim<0.0001) while haplotype C-C-A-T-C, C-C-A-C-C, T-T-A-C-C were significantly lower (Psim<0.0001). Our data suggested that the genetic variation of the rs10884402 and rs950809 in intron 1 of SORCS1 was associated with the late-onset AD in the Chinese Han population.