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Biomedical subjects

A Papassotiropoulos

Publications and source records attributed to A Papassotiropoulos.

At least 37 records · Page 2Linked to original sources
PubMed2000

Association between an interleukin-6 promoter and 3' flanking region haplotype and reduced Alzheimer's disease risk in a German population.

Several studies have demonstrated that interleukin-6 (IL-6) is involved in the pathogenesis of Alzheimer's disease (AD). We previously reported on an association between the C allele of a variable number of tandem repeat polymorphism in the 3' flanking region of IL-6 gene (IL-6vntr) and delayed initial onset and reduced AD risk. A novel G/C polymorphism at position -174 in the IL-6 gene promoter (IL-6prom) has recently been identified and appears to influence the regulation of IL-6 expression. We examined this functional polymorphism in 102 AD patients and two control groups of 191 healthy subjects and 160 depressed patients. There was no evidence for an allelic association between IL-6prom polymorphism and earlier age of onset or risk of AD. However, haplotype analysis showed a strong linkage disequilibrium between IL-6vntr and IL-6prom and demonstrated an interaction between IL-6vntr and IL-6prom which modifies AD risk.

Alleles↗
PubMed2000

Genetic association of a cystatin C gene polymorphism with late-onset Alzheimer disease.

OBJECTIVE: To determine whether the cystatin C gene (CST3) is genetically associated with late-onset Alzheimer disease (AD). DESIGN: A case-control study with 2 independent study populations of patients with AD and age-matched, cognitively normal control subjects. SETTING: The Alzheimer's Disease Research Unit at the University Hospital Hamburg-Eppendorf, Hamburg, Germany, for the initial study (n = 260). For the independent multicenter study (n = 647), an international consortium that included the Massachusetts Alzheimer's Disease Research Center at the Massachusetts General Hospital, Boston; the Scientific Institute for Research and Patient Care, Brescia, Italy; and Alzheimer's research units at the Universities of Basel and Zurich, Switzerland, and Bonn, Goettingen, and Hamburg, Germany. PARTICIPANTS: Five hundred seventeen patients with AD and 390 control subjects. MEASURES: Molecular testing of the KspI polymorphisms in the 5' flanking region and exon 1 of CST3 and the apolipoprotein E (APOE) genotype. Mini-Mental State Examination scores for both patients with AD and control subjects. RESULTS: Homozygosity for haplotype B of CST3 was significantly associated with late-onset AD in both study populations, with an odds ratio of 3.8 (95% confidence interval, 1.56-9.25) in the combined data set; heterozygosity was not associated with an increased risk. The odds ratios for CST3 B/B increased from 2.6 in those younger than 75 years to 8.8 for those aged 75 years and older. The association of CST3 B/B with AD was independent of APOE epsilon4; both genotypes independently reduced disease-free survival. CONCLUSIONS: CST3 is a susceptibility gene for late-onset AD, especially in patients aged 75 years and older. To our knowledge, CST3 B is the first autosomal recessive risk allele in late-onset AD.

Age of Onset↗
PubMed2000

Distinction of early- and late-onset depression in the elderly by their lifetime symptomatology.

OBJECTIVE: It has been proposed that early-onset depression (EOD) and late-onset depression (LOD) differ etiologically and phenomenologically. To validate the phenomenological distinction, the affective symptoms of elderly subjects with EOD and LOD were compared. METHODS: Seventy-one patients with age-at-onset of depression below 60 years (EOD) and 67 age-matched patients with age-at-onset above 60 years (LOD) were consecutively recruited from the Departments of Psychiatry of the University of Mainz and the University of Bonn. To reduce the effect of interepisode variance of symptoms, we focused on the lifetime prevalence of different affective symptoms which were evaluated using the Composite International Diagnostic Interview (CIDI). Logistic regression analysis was performed to identify particular depressive symptoms which might discriminate EOD and LOD, and to account for possible sociodemographic differences between the two groups. RESULTS AND CONCLUSION: Low spirits and feelings of worthlessness were more frequently found in EOD, they were sufficient discriminators to distinguish elderly subjects with EOD and LOD. This study provides further evidence for a phenomenological distinction between early- and late-onset depression in the elderly.

Affect↗
PubMed2000

The concreteness effect: evidence for dual coding and context availability.

The term concreteness effect refers to the observation that concrete nouns are processed faster and more accurately than abstract nouns in a variety of cognitive tasks. Two models have been proposed to explain the neuronal basis of the concreteness effect. The dual-coding theory attributes the advantage to the access of a right hemisphere image based system in addition to a verbal system by concrete words. The context availability theory argues that concrete words activate a broader contextual verbal support, which results in faster processing, but do not access a distinct image based system. We used event-related fMRI to detect the brain regions that subserve to the concreteness effect. We found greater activation in the lower right and left parietal lobes, in the left inferior frontal lobe and in the precuneus during encoding of concrete compared to abstract nouns. This makes a single exclusive theory unlikely and rather suggests a combination of both models. Superior encoding of concrete words in the present study may result from (1) greater verbal context resources reflected by the activation of left parietal and frontal associative areas, and (2) the additional activation of a non-verbal, perhaps spatial imagery-based system, in the right parietal lobe.

Adult↗
PubMed2000

Subthreshold depressive and anxiety disorders in the elderly.

The aims of the present study were to compare the current and lifetime prevalences for major and subthreshold affective disorders in elderly subjects in the general population, to assess the influence of demographic variables on prevalence rates, and to examine co-morbidity between these disorders. Major and subthreshold disorders were diagnosed in 286 subjects (aged >/= 60 years). Four-point-nine percent of the subjects had a lifetime diagnosis of major depression, 31.8% either minor or recurrent brief depression, 6.6% a major anxiety disorder, and 18.5% a subthreshold anxiety disorder. The risk for current and lifetime subthreshold anxiety was higher in females than in males, the lifetime prevalence for subthreshold anxiety disorders was increased in elderly subjects and subjects with low professional levels. Increased co-morbidity between major and subthreshold depressive and anxiety disorders could not be observed. In the elderly, subthreshold depressive and anxiety disorders are frequent, more so than major affective disorders. The presence of subthreshold anxiety disorders, but not subthreshold depression, is influenced by age, gender, and previous professional level. Further research focusing on detection, evaluation of risk factors and the relevance for the quality of life in the elderly general population is needed.

Aged↗
PubMed2000

Advanced parental age: a risk factor for Alzheimer's disease or depression in the elderly?

BACKGROUND: Advanced parental age has been suggested as a risk factor for Alzheimer's disease (AD) as well as for other psychiatric disorders. In the present investigation, a sample of gerontopsychiatric patients was examined for a possible parental age effect. STUDY POPULATION AND METHODS: Eighty-three patients with AD, 154 elderly patients with depressive episodes, and 48 comorbid patients (AD and depressive episode) as well as 107 age-matched healthy control subjects from the general population were included in the investigation. Information on the years of birth of the parents was derived from personal or family history information. RESULTS: The mean maternal and paternal ages at the time of birth of the index subject were not significantly different for the different diagnostic subgroups or for the control sample. CONCLUSION: There was no evidence in our sample that advanced parental age increases the risk of AD or depression in the elderly.

Aged↗
PubMed2000

Confirmation of the association between bleomycin hydrolase genotype and Alzheimer's disease.

Bleomycin hydrolase (BH), a cysteine protease from the papain superfamily, is considered to be a candidate for the beta-secretase, which is presumably involved in the production of beta-amyloid peptide. The G/G genotype of BH was identified as a significant risk factor for the development of Alzheimer's disease (AD) in subjects not carrying the apolipoprotein E epsilon4 allele (apoE-epsilon4). However, this finding was recently challenged. We studied this polymorphism in a homogenous sample of German AD patients and controls. The over-representation of the G/G genotype in AD patients could be confirmed, however it was more pronounced in apoE-epsilon4 carriers. Additional studies should be undertaken to increase the confidence that the BH polymorphism is associated with AD and to explore the relationship between BH and apoE.

Aged↗
PubMed2000

New insights into the metabolic consequences of large-scale mtDNA deletions: a quantitative analysis of biochemical, morphological, and genetic findings in human skeletal muscle.

In order to study putative genotype phenotype correlations in mitochondrial disorders due to large-scale mtDNA deletions we performed a quantitative analysis of biochemical, morphological, and genetic findings in 20 patients. The size of the mtDNA deletions varied from 2 to 7.5 kb with a degree of heteroplasmy ranging from 16% to 78%. Applying improved methods for measuring respiratory chain enzyme activities, we found highly significant inverse correlations between the percentage of cytochrome c oxidase (COX)- negative fibers and citrate synthase (CS) normalized COX ratios. Significant correlations were also established between CS normalized complex I and complex IV ratios as well as between the degree of heteroplasmy of mtDNA deletions and the percentage of ragged red fibers, COX-negative fibers, and CS normalized complex I and complex IV ratios. Our results indicate that the degree of heteroplasmy of mtDNA deletions is mirrored on the histological as well as the biochemical level. Furthermore, our findings suggest that single large-scale deletions equally influence the activities of all mitochondrially encoded respiratory chain enzymes. Even low degrees of heteroplasmy of mtDNA deletions were found to result in biochemical abnormalities indicating the absence of any well-defined mtDNA deletion threshold in skeletal muscle.

Adolescent↗
PubMed2000

No association between an intronic biallelic polymorphism of the FE65 gene and Alzheimer's disease.

The cleavage of the amyloid precursor protein (APP) into amyloidogenic components (Abeta) is a central event in the pathogenesis of Alzheimer's disease (AD). FE65 is a protein that is involved in APP metabolism and may facilitate the production of Abeta. Recently, an intronic polymorphism of the gene encoding FE65 (FE65) was associated with altered risk for the development of sporadic AD. In our sample of 102 AD patients and 351 non-demented controls we did not replicate the association between FE65 and AD. Moreover, we observed no risk-modifying interaction and no linkage disequilibrium between FE65 and the gene encoding the acid protease cathepsin D (catD), which - like FE65 - is involved in APP metabolism and is also located on chromosome 11p15. We conclude that, whereas FE65 is implicated in AD pathology, the gene encoding FE65 does not appear to confer a substantial risk for AD.

Aged↗
PubMed2000

Plasma 24S-hydroxycholesterol (cerebrosterol) is increased in Alzheimer and vascular demented patients.

Alzheimer's disease (AD) is characterized by the presence of senile plaques, neurofibrillary tangles, and neuronal cell loss associated with membrane cholesterol release. 24S-hydroxycholesterol (24S-OH-Chol) is an enzymatically oxidized product of cholesterol mainly synthesized in the brain. We tested the hypothesis that plasma levels of this oxysterol could be used as a putative biochemical marker for an altered cholesterol homeostasis in the brain of AD patients. Thirty patients with clinical criteria for AD, 30 healthy volunteers, 18 depressed patients, and 12 patients with vascular dementia (non-Alzheimer demented) were studied. Plasma concentrations of 24S-OH-Chol were assayed by isotope dilution;-mass spectrometry, cholesterol was measured enzymatically, and apolipoprotein E (apoE) was genotyped by polymerase chain reaction and restricted fragment length polymorphism. The concentration of 24S-OH-Chol in AD and non-Alzheimer demented patients was modestly but significantly higher than in healthy controls and in depressed patients. There was no significant difference in the concentrations of 24S-OH-Chol between depressed patients and healthy controls nor between AD and non-Alzheimer demented patients. The apoE straightepsilon4 allele influences plasma 24S-OH-Chol. However, this influence could be completely accounted for by the elevated plasma cholesterol in apoE4 hetero- or homozygotes. Plasma 24S-OH-Chol levels correlated negatively with the severity of dementia. AD and vascular demented patients appear to have higher circulating levels of 24S-OH-Chol than depressed patients and healthy controls. We speculate that 24S-OH-Chol plasma levels may potentially be used as an early biochemical marker for an altered cholesterol homeostasis in the central nervous system. 24S-hydroxycholesterol (cerebrosterol) is increased in Alzheimer and vascular demented patients.

Aged↗
PubMed2000

A genetic variation of cathepsin D is a major risk factor for Alzheimer's disease.

Cathepsin D (catD) is an intracellular acid protease possibly involved in Alzheimer's disease (AD)-related neurodegeneration through cleavage of amyloid precursor protein into amyloidogenic components. We studied whether an exonic polymorphism of the catD gene (C --> T [Ala --> Val] transition at position 224), which possibly influences pro-catD secretion and intracellular maturation of the enzyme, was associated with the risk for the development of AD in 127 demented patients and 184 controls. The catD*T allele was significantly overrepresented in demented patients (11.8%) compared with nondemented controls (4.9%). Carriers of the catD*T allele had a 3.1-fold increased risk for developing AD than noncarriers. Carriers of the apolipoprotein E (ApoE) epsilon4 allele (ApoE*4) had a 3.9-fold increased risk than non-carriers. The adjusted odds ratio for subjects with the ApoE*4 and the catD*T allele was 19.0 compared with subjects with neither of these two alleles. Our data confirm the results of a recently performed pilot study in an independent sample and suggest that the catD genotype is strongly associated with the risk for AD.

Aged↗
PubMed1999

No association between an intronic polymorphism in the presenilin-1 gene and Alzheimer disease in a German population.

A polymorphism in intron 8 of the presenilin-1 (PS-1) gene has been demonstrated to increase the risk for developing late-onset Alzheimer disease (AD). Conflicting results exist for the association between this intronic polymorphism and AD probably due to variations in the PS-1 gene among different ethnic groups. We investigated the genetic association between this intronic polymorphism in the PS-1 gene and AD in a homogenous group of German Caucasians. The control group consisted of healthy subjects and depressed patients. There were no significant differences in the distribution of the PS-1 genotypes and allele frequencies between AD patients and controls. Our data do not support an association between the intronic polymorphism of the PS-1 gene and AD and there was no interaction between the PS-1 genotype and apolipoprotein E epsilon4 allele.

Aged↗
PubMed1999

Allelic variants of dopamine receptor D4 (DRD4) and serotonin receptor 5HT2c (HTR2c) and temperament factors: replication tests.

The contribution of genetic factors to personality differences between individuals is evidenced by twin and adoption studies. Ebstein et al. [1996, 1997a, 1997b] reported an association between the long repeat allele of the dopamine D4-exon-III receptor polymorphism and the human personality dimension novelty seeking (NS), between the 5HT2c-ser-23 allele and reward dependence, and an interaction between both receptor polymorphisms and reward dependence. Subsequent replication tests mainly reported controversial results for the association between DRD4-exon-III long repeat and NS. We examined a homogeneous study population of 190 healthy male students of middle European descent, aged between 20 and 30 years using Cloninger's TPQ in order to replicate Ebstein's findings. Using a significance level of 1%, no association between the long repeat of the DRD4-exon-III polymorphism and NS and between the 5HT2c receptor polymorphism and reward dependence was found, but a significant interaction effect of DRD4 and 5HT2c receptor polymorphisms on reward dependence was observed in accordance to Ebstein's report.

Adult↗
PubMed1999

Genetic polymorphism of cathepsin D is strongly associated with the risk for developing sporadic Alzheimer's disease.

The beta amyloid peptide derives from its precursor protein via proteolytic cleavage of yet unidentified proteases (beta- and gamma-secretases). Cathepsin D is an intracellular protease with in-vitro beta-secretase-like features. An exonic polymorphism of the cathepsin D gene (alanine to valine transition at position 224, exon 2) has been associated with altered enzyme function. We tested the hypothesis that this polymorphism is associated with an increased risk for Alzheimer's disease in 102 demented patients, 191 healthy subjects, and 160 depressed patients. There was a highly significant overrepresentation of the cathepsin D*T allele in demented patients (14.2%) compared to non-demented controls (6.7%, P = 0.0012). Carriers of the cathepsin D*T allele had a 2.4-fold increased risk for developing AD than non-carriers. Carriers of the apolipoprotein E epsilon 4 allele had a 4.1 -fold increased risk than non-carriers. The odds ratio for subjects with the apolipoprotein E epsilon 4 and the cathepsin D*T allele was 5.9. Our data suggest that the cathepsin D genotype is strongly associated with the risk for Alzheimer's disease.

Aged↗
PubMed1999

Functional MRI of cerebral activation during encoding and retrieval of words.

The aims of the present study were to identify the cerebral structures associated with encoding and retrieval of verbal material. To circumvent the inherent disadvantages of the conventional block designs used in functional magnetic resonance imaging (MRI), an event-related design compared activation related to randomly intermixed old and new words during recognition. To support the validity of results, both nonparametric analyses in regions of interest (ROI) and statistical parametric mapping (SPM 96) were used. Twelve healthy volunteers, ages 22-35 years, performed three tasks: intentional encoding of words, recognition of old (previously learned) words, and discrimination between words and nonwords, a task to control for visual input and motor output during recognition. Echo-planar magnetic resonance imaging of blood-level, oxygen-dependent, task-related changes was used to compare cerebral activity under active and resting conditions as well as to detect event-related activity within blocks of trials. Comparable results were obtained following nonparametric statistical analysis of selected ROI and SPM. Encoding of words was associated with increased activity in the left inferior frontal gyrus, including Broca's area and in the left parietal association cortex. Event-related data analysis revealed activation of the right medial frontal gyrus, the right anterior cingulate gyrus, and parietal association cortices during recognition of previously presented words. In the lexical decision task, words in comparison with nonwords were associated with activation of the left parietal association cortex. The right medial frontal gyrus, the right anterior cingulate gyrus, and the right parietal association cortex are likely to be involved in episodic memory functions during recognition of previously presented verbal material. The comparison of event-related activation occurring within one trial block instead of among several trial blocks may significantly improve the performance of memory studies.

Adult↗
PubMed1999

A genetic variation of the inflammatory cytokine interleukin-6 delays the initial onset and reduces the risk for sporadic Alzheimer's disease.

Local inflammatory processes surrounding the amyloid plaques contribute to the progression and acceleration of the Alzheimer's disease (AD)-related neurodegeneration. Interleukin-6 (IL-6) is an inflammatory cytokine with possible involvement in the local immune response occurring in the central nervous system of AD patients. We tested the hypothesis as to whether a genetic polymorphism of the IL-6 gene (IL-6) modifies the age at onset and risk for sporadic AD. Our results support an association of the C allele of the IL-6 genotype with a delayed initial onset and reduced disease risk and indicate that genetically determined alterations of the immune response may modify the course of AD.

Age of Onset↗