Genetic Variation in the α7 Nicotinic Acetylcholine Receptor is Associated with Delusional Symptoms in Alzheimer’s Disease

Psychotic symptoms are common in Alzheimer’s disease (AD) and have a negative impact on quality of life. It is suggested that psychotic symptoms may be attributed to genetic risk factors which are revealed during neurodegeneration. CHRNA7, the gene for the α7 nicotinic acetylcholine receptor, has been associated with schizophrenia in linkage and association studies. Hence we investigated single SNPs and haplotypes in CHRNA7 in relation to AD with psychosis in a large, well-characterised and previously described cohort within the Northern Ireland population. A significant association between delusions and the T allele of rs6494223 (P = 0.014, OR = 1.63, CI = 1.22–2.17) was found. This suggests that the α7 receptor may be a suitable target for the treatment of AD with psychosis.     

The CLU Gene rs11136000 Variant is Significantly Associated with Alzheimer’s Disease in Caucasian and Asian Populations

Large-scale genomewide association studies have reported that the CLU rs11136000 polymorphism is significantly associated with Alzheimer’s disease (AD) in people of Caucasian ancestry. Recently, this association was investigated in Asian populations (Chinese, Japanese, and Korean). However, these studies reported either a weak association or no association between the rs11136000 polymorphism and AD. We believe that this discrepancy may be caused by the relatively small sample size of the previous studies and the genetic heterogeneity of the rs11136000 polymorphism in AD among different populations. For this study, we searched the PubMed and AlzGene databases. We selected 18 independent studies (6 studies of Asian populations and 12 of populations of Caucasian ancestry) that evaluated the association between the rs11136000 polymorphism and AD using a case–control experimental design. We evaluated the genetic heterogeneity of the rs11136000 polymorphism in Caucasian and Asian populations. We then investigated the rs11136000 polymorphism by a meta-analysis in Asian populations using allele, dominant, and recessive models. We identified a significant association between rs11136000 and AD with the allele model (P = 2.00 × 10^?4) and the dominant model (P = 5.00 × 10^?3). Meanwhile, a similar genetic risk of the rs11136000 polymorphism in AD was observed in Asian and Caucasian populations. Further meta-analysis in pooled Asian and Caucasian populations indicated a more significant association with the allele (P = 8.30 × 10^?24), dominant (P = 4.46 × 10^?17), and recessive (P = 3.92 × 10^?12) models. Collectively, our findings from this meta-analysis indicate that the effect of the CLU rs11136000 polymorphism on AD risk in Asian cohorts (Chinese, Japanese, and Korean) is consistent with the protective effect observed in Caucasian AD cohorts.     

A Comparative Study of the Use and Understanding of Self-Presentational Display Rules in Children with High Functioning Autism and Asperger’s Disorder

The use and understanding of self-presentational display rules (SPDRs) was investigated in 21 children with high-functioning autism (HFA), 18 children with Asperger's disorder (AspD) and 20 typically developing (TD) children (all male, aged 4- to 11-years, matched on mental age). Their behaviour was coded during a deception scenario to assess use of SPDRs; understanding of SPDRs was assessed via three real/apparent emotion-understanding vignettes. The children with HFA and AspD used less effective SPDRs than the TD children, but there were no group differences in understanding SPDRs. The children with HFA and AspD did not differ on their use or understanding of SPDRs, and the results are discussed in relation to the similarities and differences between these diagnostic conditions.     

α-T-catenin is expressed in human brain and interacts with the Wnt signaling pathway but is not responsible for linkage to chromosome 10 in Alzheimer’s disease

The gene encoding α-T-catenin, CTNNA3, is positioned within a region on chromosome 10, showing strong evidence of linkage to Alzheimer’s disease (AD), and is therefore a good positional candidate gene for this disorder. We have demonstrated that α-T-catenin is expressed in human brain, and like other α-catenins, it inhibits Wnt signaling and is therefore also a functional candidate. We initially genotyped two single-nucleotide polymorphisms (SNPs) in the gene, in four independent samples comprising over 1200 cases and controls but failed to detect an association with either SNP. Similarly, we found no evidence for association between CTNNA3 and AD in a sample of subjects showing linkage to chromosome 10, nor were these SNPs associated with Aβ deposition in brain. To comprehensively screen the gene, we genotyped 30 additional SNPs in a subset of the cases and controls (n>700). None of these SNPs was associated with disease. Although an excellent candidate, we conclude that CTNNA3 is unlikely to account for the AD susceptibility locus on chromosome 10.     

LRRK2 G2019S and R1441G mutations associated with Parkinson’s disease are common in the Basque Country, but relative prevalence is determined by ethnicity

Mutations in LRRK2 gene are the most frequent cause of Parkinson’s disease (PD) described, but their prevalence varies between populations. Patients, 418, with PD and 138 unrelated controls from the Basque Country were screened for LRRK2 G2019S and R1441G mutations. Of the patients, 3.82% were heterozygous carriers of G2019S and 13.15% of R1441G. G2019S frequency was higher in non-Basque population (6.0%), while R1441G was more common in Basque origin population (22.4%). Our conclusion is that both G2019S and R1441G mutations’ frequency varies markedly between Basque and non-Basque origin population reinforcing the importance of ethnicity consideration when establishing mutation prevalence. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.