Genetic risk factors and markers for Alzheimer’s disease and/or depression in the VITA study

Grünblatt, Edna; Zehetmayer, Sonja; Bartl, Jasmin; Löffler, Christiane; Wichart, Ildiko; Rainer, Michael; Jungwirth, Susanne; Bauer, Péter; Danielczyk, W; Tragl, Karl-Heinz; Riederer, Peter; Fischer, Peter

doi:10.1016/j.jpsychires.2008.05.008

Cited by 51 publications

(36 citation statements)

References 113 publications

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“…The metaanalysis estimates and tests for heterogeneity are provided in tables 1-3 . As has been observed in the general population, the prevalence varied by geographic location, with the lowest regional estimates for the prevalence of e4 carriers in Asia: 41 * Significant heterogeneity at p < 0.10; ** significant heterogeneity at p < 0.01. NR = Not reported.…”

Section: Study Characteristicsmentioning

confidence: 62%

Prevalence of Apolipoprotein E4 Genotype and Homozygotes (APOE e4/4) among Patients Diagnosed with Alzheimer’s Disease: A Systematic Review and Meta-Analysis

et al. 2011

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Background: Population allele frequencies of apolipoprotein E (APOE) vary by geographic region. The purpose of this study is to summarize and evaluate published estimates for the prevalence of APOE e4 carrier status among the population diagnosed with Alzheimer’s disease (AD) by geographic region and country. Methods: A systematic review of English-language publications from January 1, 1985, through May 31, 2010, was conducted. Studies reporting APOE e4 status for patients diagnosed with AD were included in the analysis; trials and autopsies were excluded. APOE e4 data were pooled, and prevalence and 95% confidence intervals (CIs) were calculated. Results: Pooled estimates for APOE e4 carrier prevalence data were derived from 142 independent samples: 48.7% (95% CI: 46.5–51.0), and from 73 samples for e4/4 (homozygotes): 9.6% (95% CI: 8.4–10.8). The highest estimates were in Northern Europe: 61.3% (95% CI: 55.9–66.7), e4/4 prevalence: 14.1% (95% CI: 12.2–16.0). The lowest estimates were in Asia and Southern Europe. Substantial heterogeneity of these prevalence estimates was observed. Conclusions: APOE e4 genotype prevalence varies among AD patients by region and within each country. Further exploration is warranted to better understand the substantial heterogeneity of these prevalence estimates.

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Section: Study Characteristicsmentioning

confidence: 62%

Prevalence of Apolipoprotein E4 Genotype and Homozygotes (APOE e4/4) among Patients Diagnosed with Alzheimer’s Disease: A Systematic Review and Meta-Analysis

et al. 2011

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“…Quaranta et al [19] demonstrated that the risk of psychosis is increased in individuals with the 5-HTT-LPR L allele, and Sukonick et al [15] and Sweet et al [16] reported that the L allele is significantly associated with aggression in AD. Conversely, other studies did not find significant associations between 5-HTT-LPR polymorphisms and neuropsychiatric symptoms in AD [21,22,23,24,25,26,27,28] (online suppl. table 1).…”

Section: Discussionmentioning

confidence: 83%

“…Several studies showed that 5-HTT-LPR genotypes are associated with neuropsychiatric symptoms in AD [15,16,17,18,19,20], whereas other studies did not replicate associations of 5-HTT-LPR polymorphisms with neuropsychiatric symptoms [21,22,23,24,25,26,27,28]. Although previous studies consistently demonstrated that SLC6A4 mRNA levels in leukocytes are significantly higher in patients with MDD compared to healthy controls [29,30], the mRNA expression level in leukocytes from AD patients has not been examined yet.…”

Section: Introductionmentioning

confidence: 99%

Association Study and Meta-Analysis of Polymorphisms, Methylation Profiles, and Peripheral mRNA Expression of the Serotonin Transporter Gene in Patients with Alzheimer's Disease

Yamazaki

Yoshino²,

Mori³

et al. 2016

Dement Geriatr Cogn Disord

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Background/Aim: The aim of this study was to elucidate the relationship between Alzheimer's disease (AD) and the serotonin transporter gene (SLC6A4). Methods: AD subjects (n = 43) and controls (n = 47) were recruited and evaluated. In leukocytes, we evaluated two polymorphisms in SLC6A4, the serotonin transporter length polymorphic region (5-HTT-LPR) and rs25531, as well as methylation rates of the SLC6A4 promoter region and the SLC6A4 mRNA expression level. We also performed a meta-analysis to examine the relationship between the frequency of the L allele and the risk of AD. Results: The distributions of 5-HTT-LPR and rs25531 polymorphisms in AD subjects were not different from those of controls. Although the methylation rates in AD subjects were not significantly different from those of controls, the expression level in AD subjects was significantly higher than in controls. Additionally, the expression level in AD subjects was significantly correlated with apathy. Meta-analysis revealed that the L/L genotype significantly reduced the risk of AD, but only in the Caucasian population. Conclusion: Higher SLC6A4 mRNA expression in leukocytes in AD was associated with apathy regardless of SLC6A4 genotypes and methylation rates of the promoter region. The L/L genotype may reduce the risk of AD in the Caucasian population.

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“…Among the nongenetic risk factors, advanced age plays a major role in LOAD, reflected by the steep increase in prevalence from the age of 65 on [Prince and Jackson, 2009]. Also, a history of depression (DE), particularly late-life DE, is known to increase the risk of AD [Grünblatt et al, 2009;Barnes et al, 2012;Mossaheb et al, 2012]. Unipolar DE is the most frequent of the mood disorders, which taken together have a 12-month prevalence of almost 10% [Kessler et al, 2005].…”

Section: Introductionmentioning

confidence: 99%

“…As a consequence, polymorphisms that are predisposing to DE might display an independent association signal with LOAD. In the present study, we aimed at characterizing this pleiotropic effect for both the triallelic serotonin transporter gene-linked polymorphic region (5HTTLPR), and the MAOAupstream variable number of tandem repeats (MAOA-uVNTR) in participants of the Vienna Transdanube Aging (VITA) study, since these two polymorphisms have been proposed to play a role in AD and DE in prospective studies (detailed overview see Supplementary Table S1) Previous studies have addressed similar issues in the same sample, but restricted their analyses to the biallelic 5HTTLPR and its influence on LOAD and DE diagnoses up to the first follow-up [Grünblatt et al, 2006b[Grünblatt et al, , 2009. In this study, we used diagnoses up to the latest follow-up data available, corresponding to examination of the third follow-up at a mean age of 82.5 years.…”

Section: Introductionmentioning

confidence: 99%

Investigation of association of serotonin transporter and monoamine oxidase‐A genes with Alzheimer's disease and depression in the VITA study cohort: A 90‐month longitudinal study

Scholz

Jungwirth

Danielczyk

et al. 2014

American J of Med Genetics Pt B

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Alzheimer's disease (AD) and depression (DE) are common psychiatric disorders strongly intertwined with one another. Nevertheless, etiology and early diagnosis of the disorders are still elusive. Several genetic variations have been suggested to associate with AD and DE, particularly in genes involved in the serotonergic system such as the serotonin transporter (SERT/SLC6A4), responsible for the removal from the synaptic cleft, and the monoamine-oxidase-A (MAOA), responsible for the presynaptic degradation of serotonin. Here, we attempt to characterize this pleiotropic effect for the triallelic SERT gene-linked polymorphic region (5HTTLPR) and for the MAOA-uVNTR, in participants in the Vienna-Transdanube-Aging (VITA)-study. The VITA-study is a community-based longitudinal study following a birth cohort (75 years old at baseline examination, n = 606) from Vienna for a period of 90 months with a regular follow-up interval of 30 months. Our main finding, confirming previous reports, is that the 5HTTLPR S-allele is a risk allele for DE (OR = 1.55 CI 95% 1.03-2.32) and its carriers had a steeper increase in SGDS sum score. No association to AD was found. MAOA-uVNTR did not associate with either AD or DE. However, in AD MAOA-uVNTR S-allele carriers a steeper increase of HAMD and STAI1 sum scores (P < 0.05) was observed. Although the VITA-study cohort is rather small with low power to detect gene alterations, the uniqueness of this very thoroughly investigated and homogenous cohort strengthens the results through exceptional data collection. Still, reinvestigation in a larger cohort similar to this, as well as a meta-analysis, is important to confirm these results.

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Genetic risk factors and markers for Alzheimer’s disease and/or depression in the VITA study

Cited by 51 publications

References 113 publications

Prevalence of Apolipoprotein E4 Genotype and Homozygotes (APOE e4/4) among Patients Diagnosed with Alzheimer’s Disease: A Systematic Review and Meta-Analysis

Prevalence of Apolipoprotein E4 Genotype and Homozygotes (APOE e4/4) among Patients Diagnosed with Alzheimer’s Disease: A Systematic Review and Meta-Analysis

Association Study and Meta-Analysis of Polymorphisms, Methylation Profiles, and Peripheral mRNA Expression of the Serotonin Transporter Gene in Patients with Alzheimer's Disease

Investigation of association of serotonin transporter and monoamine oxidase‐A genes with Alzheimer's disease and depression in the VITA study cohort: A 90‐month longitudinal study

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