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Purpose: Recently, a large genome-wide association study has revealed that polymorphism of alleles and genotypes in rs3,764,650 within ABCA7 gene is associated with Alzheimer disease in whites. We conducted a case-control study to investigate whether these susceptible genetic variants are risk factors for sporadic Alzheimer disease (SAD) in Chinese Han population., Design and Methods: A total of 633 participants consisting of 350 SAD and 283 nondemented elderly controls matched for sex and age were recruited and genetic variants in ABCA7 (rs3,764,650) were genotyped using DNA sequencing., Results: On the basis of allele and genotype frequencies in both groups, we found a significant association (P=0.004) between ABCA7 genotypes and SAD in Chinese Han population, and the results were influenced by age and ApoEε4 status. ApoEε4-carrier and aging are linked to enhancing ABCA7 risk-associated SAD. However, the prevalence of the minor allele G in rs3,764,650 within ABCA7 showed no significant difference between the 2 groups in this study., Conclusions: ABCA7 (rs3,764,650) was associated with SAD in the Chinese population, with both ApoEε4-carrier and aging being factors enhancing its risk.

Background/aims: As a suitable test to screen for Alzheimer's disease (AD) or mild cognitive impairment (MCI), studies to validate the Chinese version of Addenbrooke's 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 Cronbach's 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 (Cronbach's 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.

CD33 and MS4A6A genes play potential key roles in the pathogenesis of Alzheimer's disease (AD). One recent genome-wide association study has revealed that the rs3865444 polymorphism in the CD33 gene and rs610932 polymorphism in the MS4A6A gene are associated with susceptibility to AD in Caucasians. To evaluate the relationship between the polymorphism of the CD33, MS4A6A gene and AD in the ethnic Chinese Han, we conducted a case-control study (n = 383, age > 54) to determine the prevalence of single-nucleotide polymorphism of two genes in patients with AD in Chinese population of Mainland, and clarified whether these polymorphisms are risk factors for AD. The prevalence of the allele (T) in the rs3865444 polymorphism of the CD33 gene and allele (C) in rs610932 polymorphism of the MS4A6A gene was significantly different in AD patients and control subjects (P < 0.001, respectively), and the results were not influenced by age, gender, or APOE status. Our data revealed the allele (T) of the rs3865444 polymorphism of the CD33 gene and the allele (C) of the rs610932 polymorphism of the MS4A6A gene may contribute to AD risk in the Chinese Han population.

Purpose: To assess genetic variations of GAB2 as a risk factor for developing Alzheimer disease (AD)., Design and Methods: A case-control study (n=310; age>50 y) was conducted to determine the prevalence of 5 single nucleotide polymorphisms (SNPs) of GAB2 (rs2373115, rs1385600, rs4945261, rs7101429, and rs7115850) in patients with AD in Chinese population of mainland China, and was investigated whether these polymorphisms are risk factors for AD., Results: Our results supported a possible implication of 3 tested SNPs of GAB2 (rs4945261, rs7101429, and rs7115850) in AD in the ethnic Chinese Han, of which the maximal significance of association was at SNP rs7101429 C allele (P=4.0×10; odds ratio=2.0; 95% confidence interval, 1.4-2.8), and this observed association was not affected by APOEε4 genotype. In the haplotypes analysis, the minor alleles of the 3 tested SNPs were composed of a TCG haplotype, which had a significant difference in haplotype distribution between the 2 groups (P=3.4×10; odds ratio=8.32; 95% confidence interval, 4.57-15.14)., Conclusions: Our findings implicate an association between genetic variations of GAB2 and AD in Han Chinese, and the minor alleles of the 3 tested SNPs (rs4945261, rs7101429, and rs7115850) might increase the risk of AD.

Background: LRP2 (also called megalin) plays a potential key role in the pathogenesis of Alzheimer's 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., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Background: Transthyretin-related hereditary amyloidosis is an autosomal dominant inherited disease caused by mutations in the transthyretin (TTR) gene. Corresponding to the various transthyretin gene mutations and a wide range of geographical distribution, transthyretin-related hereditary amyloidosis presents diverse characteristics in genotype-phenotype correlation., Objective/method: Here, we identify the clinical characteristics of a Chinese family affected by transthyretin-related hereditary amyloidosis with TTR Tyr114Cys mutation., Results/conclusion: The pathogenic mechanism studies showed that the protein encoded by TTR Tyr114Cys is more easily depolymerized to form amyloid fibrils. Moreover, the cytotoxicity of the TTR Tyr114Cys may be attributed to its ability to persistently activate the extracellular-signal-regulated kinase 1/2 pathway., (Copyright © 2010 S. Karger AG, Basel.)

We conducted a case-control study to determine the prevalence of the CALHM1 P86L polymorphism (rs2986017) in patients with Alzheimer's 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.