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Since ethanol and its metabolite, acetaldehyde, are directly neurotoxic, alcohol intake could affect the development of Alzheimer's disease (AD). Mitochondrial aldehyde dehydrogenase 2 (ALDH2) metabolizes acetaldehyde into acetate and also protects against oxidative stress, playing an important role in the development of AD. The activity of dopamine β hydroxylase (DBH) is reduced in the hippocampus and neocortex in the AD brain. DBH is also involved in the pathophysiology of alcoholism. The aim of this study was to investigate whether polymorphisms of both ALDH2 and DBH genes were associated with AD. ALDH2*2 and two functional single nucleotide polymorphisms (SNPs) of the DBH gene were analyzed using a case-control study design. Our case-control data set consisted of 201 AD patients and 130 age-matched controls. We also analyzed stratifying by alcohol consumption and apolipoprotein E (APOE) genotypes. There were no associations between the SNPs studied here and the onset of AD. No synergetic associations were found among the SNPs, APOE and the risk for AD. Although high alcohol consumption AD (HAC-AD) patients were analyzed in detail, the current three SNPs were not related with HAC-AD. ALDH2*2 and functional SNPs of the DBH gene did not modify the risk for AD. Since our data set was constructed only with AD in a Japanese population, further detailed genetic analyses with other ethnic groups would be needed. [ABSTRACT FROM AUTHOR]

Previous papers have reported that clusterin (CLU, also called apolipoprotein J) maintains amyloid β-peptide (Aβ) solubility and protects against Aβ neurotoxicity. Recently, two large genome-wide association studies (GWAS) identified that a specific single nucleotide polymorphism (SNP) on the gene has been reported to modify the risk for Alzheimer's disease (AD). The present study aimed to investigate whether common single nucleotide polymorphisms (SNP) of the CLU gene are associated with AD. Six SNP, genotyped using TaqMan technology, were analyzed using a case-control study design. Furthermore, an analysis of the cases divided according to apolipoprotein E (APO E) status was also carried out. Our case-control dataset consisted of 180 AD patients and 130 age-matched controls. The present study failed to detect any association between the SNP of the CLU gene and AD. Although rs7982 and rs1532277 showed marginal association in the APO E4 negative group, the linkage disequilibrium analysis results suggest this to be a false positive. The negative associations were mainly the result of our small sample size. Larger genetic studies in different ethnics and future meta-analysis are needed to clarify the relationship between the CLU gene and AD. [ABSTRACT FROM AUTHOR]

Purpose: Exercise training (Ex) has antihypertensive and renal protective effects; however, the precise mechanisms remain unclear. The renal renin–angiotensin system (RAS) plays a vital role in renal function and pathology. Therefore, we investigated the effects of Ex on the renal RAS components in Dahl salt-sensitive (Dahl-S) rats. Methods: Male Dahl-S rats were divided into four groups: normal salt diet + sedentary, normal salt diet + Ex, high-salt diet (HS, 8% NaCl) + sedentary, and HS + Ex. Treadmill running was performed for 8 wk in the Ex groups. Results: Ex attenuated the HS-induced renal dysfunction and glomerular injury without causing blood pressure alterations. HS increased urinary excretion of both total and intact angiotensinogen. Ex decreased the HS-induced increased urinary excretion of total angiotensinogen. However, it did not change the HS-induced urinary excretion of intact angiotensinogen, indicating reduced intact angiotensinogen cleaving. Ex restored the HS-induced increased angiotensinogen and angiotensin II type 1 receptor expressions in the outer medulla and the HS-induced increased angiotensin-converting enzyme expression in the cortex. Ex restored the HS-induced decreased renin expression in the cortex and outer medulla, and the HS-induced decreased angiotensin-converting enzyme 2, angiotensin II type 2 receptor, and Mas receptor expressions in the outer medulla. Conclusions: Ex attenuates HS-induced renal dysfunction, glomerular injury, and renal RAS dysregulation in Dahl-S rats. [ABSTRACT FROM AUTHOR]

Background/Aims: A recent paper reported that the phospholipid transfer protein (PLTP) reduces phosphorylation of tau in human neuronal cells. In addition, patients with Alzheimer’s disease (AD) have significantly higher levels of PLTP in brain tissue and significantly lower PLTP-mediated phospholipid transfer activity in cerebrospinal fluid. PLTP also affects apolipoprotein E (APOE) secretion from glial cells. This study aimed to investigate whether single nucleotide polymorphisms (SNPs) of the PLTP gene are associated with AD. Methods: Five SNPs, genotyped using TaqMan® technology, were analyzed using a case-control study design. Furthermore, we also checked for a synergetic association between the PLTP gene, APOE and AD. Our case-control dataset consisted of 180 AD patients and 130 age-matched controls. Results: None of the SNPs showed a statistically significant association. We could not confirm any synergetic association between the SNPs and APOE in our AD patients. Conclusion: Our results indicate that there is no genetic association between PLTP and AD. Due to the relatively small sample size and the incomplete coverage of the region surrounding the PLTP gene of this study, larger genetic studies covering the entire PLTP gene region are needed. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A recent paper reported that a variant (rs2986017) of the calcium homeostasis modulator 1 (CALHM1) gene affects risk for late-onset Alzheimer's disease (AD). This study aims to investigate whether single nucleotide polymorphisms (SNPs) of the CALHM1 gene are associated with AD. SNPs in the genes of two other CALHM subtypes, CALHM2 and CALHM3, were also studied. Our study failed to detect any association between the SNPs of the three genes and AD. Although rs729211 showed marginal association in the APOE4 negative group, the linkage disequilibrium analysis results suggest this to be a false positive. [ABSTRACT FROM AUTHOR]

Alterations in lipoproteins are involved in the pathophysiology of Alzheimer's disease (AD). For sporadic AD, the Apolipoprotein E ( APOE) is recognized as a sole genetic risk factor. Apolipoprotein A1 (APOA1) has been suggested to bind amyloid β and promoter polymorphisms of the APOA1 gene were likely to affect the onset of the disease. Apolipoprotein D (APOD) expression is upregulating in AD brain and evidences showed APOD polymorphisms affect the risk for AD. The aim of this study was to investigate whether polymorphisms of both APOA1 and APOD genes are associated with early-onset AD (EOAD) and late-onset AD (LOAD). Common single nucleotide polymorphisms (SNPs) of the two genes were analyzed using a case-control study design. There were no associations between the two SNPs of the APOA1 gene and the onset of AD. No synergetic associations were found among the APOA1 SNPs, APOE and the risk for AD. Rs7659, 3′ UTR polymorphism of the APOD gene was associated with EOAD in APOEε4 (−) subgroup. We were unable to show any impact of the other two SNPs of the APOD gene on the risk for AD. Our results suggest that the variation of the APOD gene modifies the risk for AD. Further association studies for APOD 3′ UTR polymorphisms with other ethnic groups would be needed. [ABSTRACT FROM AUTHOR]

Background Globally, Alzheimer's disease ( AD) is becoming an increasing problem as the population ages, and the effects of lifestyle factors on cognitive decline need to be better understood. This study examined the effects of alcohol abstinence on cognitive decline in AD. Methods Cognitive function after alcohol abstinence was retrospectively reviewed in AD patients (high and low alcohol consumption groups) and then compared with an alcohol-naïve AD group. The alcohol-naïve AD group included 18 outpatients with no history of habitual drinking. The alcohol-abstinence AD group included 20 outpatients who stopped drinking after their diagnoses. The latter group was classified into high and low groups depending on the amount of they drank before abstinence. Cognitive function was evaluated with the Mini- Mental State Examination at baseline, 6 months, and 12 months. For statistical analyses, a repeated measures, two-factor anova and post-hoc multiple comparisons were performed using the Bonferroni method. Results There was a significant effect of time on Mini- Mental State Examination score, but there was no difference in the baseline scores of the alcohol-naïve and alcohol-abstinence AD groups. The score was significantly lower at 6 and 12 months than at baseline in the alcohol-naïve group, but no significant difference was seen in the alcohol-abstinence group. There was a significant interaction between time and alcohol consumption subgroup on the score, with no difference in baseline score between the low and high consumption groups. The score was significantly lower only in the high consumption group at 12 months. Conclusions In AD patients with a history of habitual drinking, abstinence was effective for reducing cognitive decline during the clinical course. However, such an effect was not seen in patients who had consumed high amounts of alcohol before diagnosis of AD. [ABSTRACT FROM AUTHOR]

Background/Aims: Several candidate genes were suggested to modify the susceptibility to both Alzheimer's disease (AD) and Parkinson's disease (PD). Symptoms of dementia are found in approximately 30% of PD patients. Both apolipoprotein E (APO E) and ubiquitin carboxyl-terminal esterase L1 (UCHL1) are neuropathogenic proteins for both diseases. The aim of this study was to investigate whether polymorphisms of both genes are associated with AD and PD with dementia (PDD). Methods: The APO E polymorphism and 5 common single-nucleotide polymorphisms (SNPs) of the UCHL1 gene were analyzed using a case-control study design. Results: Although APO E4 affected the onset of AD, the 5 SNPs of the UCHL1 gene were not associated with risk for AD. Linkage disequilibrium (LD) analysis of our Japanese data set showed that the SNPs of the UCHL1 gene are part of one LD block. Although one SNP, rs4861387, of the UCHL1 gene showed marginal association with PDD, we did not detect any association between the other SNPs and PDD. Conclusion: The common SNPs of UCHL1 are not major risk factors for AD. Since our analyses on PDD are preliminary, further genetic studies on APO E, UCHL1 and PD with and without dementia are needed. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aims: Ghrelin has been reported to enter the hippocampus and to bind to the neurons of the hippocampal formation. This peptide also affects neuronal glucose uptake and decreases tau hyperphosphorylation. There is increasing evidence suggesting an association between ghrelin and Alzheimer's disease (AD) pathology. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) of the ghrelin gene are associated with AD. Methods: The SNPs were genotyped using TaqMan technology and were analyzed using a case-control study design. Our case-control dataset consisted of 182 AD patients and 143 age-matched controls. Results: Hardy-Weinberg equilibrium and linkage disequilibrium analyses suggest that the region in and around the gene is highly polymorphic. One SNP, rs4684677 (Leu90Gln), showed a marginal association with age of AD onset. We did not detect any association between the other SNPs of the ghrelin gene and AD. Conclusion: There have been few genetic studies on the relationship between circulating ghrelin and functional SNPs. Further multifactorial studies are needed to clarify the relationship between ghrelin and AD. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A recent paper reported that Aβ oligomer causes neuronal cell death through the phosphatidylinositol-3-OH kinase (PI3K)- Akt-mTOR signaling pathway. Intraneuronal A&beta, a main pathological finding of Alzheimer's disease (AD), is also known as inhibiting activation of Akt. This study aims to investigate whether single nucleotide polymorphisms (SNPs) of the Akt1 gene are associated with AD. SNPs genotyped using TaqMan technology was analyzed using a case-control study design. Our case-control dataset consisted of 180 AD patients and 130 age-matched controls. Although two SNPs showed superficial positive, Hardy-Weinberg equilibrium (HWE) tests, and linkage disequilibrium (LD) analyses suggested that genetic regions of the gene are highly polymorphic. We failed to detect any synergetic association among Akt1 polymorphisms, Apolipoprotein E (APO E), and AD. Further genetic studies are needed to clarify the relationship between the Akt1 and AD. [ABSTRACT FROM AUTHOR]