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S Sorbi

Publications and source records attributed to S Sorbi.

At least 55 records · Page 3Linked to original sources
PubMed2000

Association between angiotensin-converting enzyme and Alzheimer disease.

BACKGROUND: Angiotensin-converting enzyme has been reported to show altered activity in patients with neurologic diseases. An insertion-deletion polymorphism in ACE has recently been linked to heart disease, cerebrovascular disease, and AD. OBJECTIVE: To determine whether the angiotensin-converting enzyme (ACE) is associated with risk of Alzheimer disease (AD). METHODS: We investigated the ACE polymorphism as a potential risk factor for AD in 151 patients with AD and 206 ethnically matched controls from Russia and in 236 patients with AD and 169 controls from North America by means of allele association methods and logistic regression. RESULTS: None of the ACE genotypes was associated with increased susceptibility to AD in the total sample or in subsets stratified by apolipoprotein E gene (APOE) epsilon4 status. However, the D allele was more frequent among AD cases between ages 66 and 70 years compared with controls in both the Russian (P = .02) and North American (P = .001) datasets. In this age group, the effect of D (odds ratio, 11.2; 95% confidence interval, 2.9-44.0) appeared to be independent of and equal or greater in magnitude to the effect of APOE epsilon4 (odds ratio, 7.8; 95% confidence interval, 3.5-7.4). CONCLUSIONS: Our results suggest that APOE and ACE genotypes may be independent risk factors for late-onset AD, but the ACE association needs to be confirmed in independent samples in which the time and extent of vascular cofactors can be assessed.

Aged↗
PubMed2000

Risperidone in idiopathic and symptomatic dystonia: preliminary experience.

Risperidone is a heterocyclic neuroleptic with prominent antiserotoninergic (5HT2) as well as antidopaminergic (D2) activity. We studied the efficacy of risperidone in the treatment of idiopathic and symptomatic dystonias in seven patients using the Fahn and Marsden rating scale for torsion dystonia before and after four weeks of treatment (2-6 mg/day). The twisting and involuntary movements with abnormal postures decreased in all the patients treated, with a statistically significant mean improvement (41%; p = 0.009, CI 95%). Our results suggest that risperidone is useful in idiopathic and symptomatic dystonia.

Adolescent↗
PubMed2000

Phospholipid composition and levels are not altered in fibroblasts bearing presenilin-1 mutations.

Lipid alterations have been reported in brain regions affected by Alzheimer disease (AD). The mechanisms causing these changes are poorly understood because it is difficult to study dynamic, biochemical processes in post-mortem brain. Fibroblasts derived from AD patients offer an alternative model to study disease-related alterations in lipid metabolism. Therefore, we measured the phospholipid levels and composition of fibroblasts from individuals bearing two different presenilin-1 mutations and compared these values to appropriate control fibroblasts. There were no differences between groups in phospholipid composition or in individual phospholipid levels, including the plasmalogens. Cholesterol levels and the cholesterol/phospholipid ratio were not different between presenilin-1 mutation bearing and control fibroblasts. Although these presenilin-1 mutation bearing fibroblasts have a number of biochemical changes related to AD, the absence of a change in phospholipid levels suggests that under these conditions, these cells are not useful in studying the mechanisms underlying the alterations in brain phospholipid levels associated with AD. However, these results do not preclude the possible use of other fibroblasts bearing AD-related mutations, e.g., APP mutations, to examine AD-related changes in brain lipid metabolism, or of these fibroblasts under different conditions.

Alzheimer Disease↗
PubMed2000

Music and cerebral hemodynamics.

Previous studies performed by positron emission tomography and Transcranial Doppler (TCD) found a different cerebral activation during musical stimuli in musicians compared to non-musicians. The aim of our study is to evaluate by means of TCD, possible different pattern of cerebral activation during the performance of different musical tasks in musicians, non-musicians and lyrical singers. Our findings show a left hemispheric activation in musicians and a right one in non-musicians. Preliminary data on lyrical singers' activation patterns need further confirmation with a larger population. These data could be related to a different approach to music listening in musicians (analytical) and non-musicians who are supposed to have an emotional approach to music.

Adult↗
PubMed2000

Association of early-onset Alzheimer's disease with an interleukin-1alpha gene polymorphism.

Overexpression of the pluripotent cytokine interleukin-1 (IL-1) by microglial cells correlates with formation of neuritic beta-amyloid plaques in Alzheimer's disease (AD). We evaluated polymorphisms in the genes coding for the IL-1alpha, IL-1beta, and IL-1 receptor antagonist cytokines, and tested their association with the occurrence and age at onset of sporadic AD. We found a strong association between the IL-1A T/T genotype and AD onset before 65 years of age (odds ratio, 4.86), with carriers of this genotype showing an onset of disease 9 years earlier than IL-1A C/C carriers. A weaker association with the age at onset was also shown for the IL-1B and IL-1RN genes. These data suggest either a direct effect of the IL-1 gene family, mainly IL-1A, on the clinical onset of AD, or a linkage dysequilibrium with an unknown locus relevant to AD on chromosome 2.

Adult↗
PubMed1999

5-HT2A receptor gene polymorphisms in anorexia nervosa and bulimia nervosa.

To examine the distribution of different polymorphisms in genes of the 5-HT system in patients with anorexia nervosa (AN) and bulimia nervosa (BN), we analyzed the distribution of a polymorphism (-1438G/A) and the presence of known mutations in 5-HT2A and 5-HT2C receptor genes in 168 Italian female patients affected by AN and BN. Patients with AN restricting type (ANr) only, unlike those with AN binge eating/purging type (ANp) and BN purging type (BNp), showed a statistically significant difference in 5-HT2A-1438A/A genotype frequency with respect to controls. With regard to the other polymorphisms, no differences were found in the studied groups with respect to controls. 5-HT2A promoter polymorphism is probably implicated in the susceptibility to eating disorders and its involvement is more significant in ANr, when compared with ANp and BNp.

Adolescent↗
PubMed1999

Association of the estrogen receptor alpha gene polymorphisms with sporadic Alzheimer's disease.

Alzheimer's disease (AD) is a multifactorial disorder determined by the interaction of genetic, metabolic, and environmental factors. In the common late-onset familial and sporadic forms of AD apolipoprotein E type 4 allele (APOE-epsilon4) is now widely accepted as a major risk factor. The association of estrogen treatment with a reduction in the risk of AD together with the modulation by estrogen of the secretory metabolism of the amyloid precursor protein offers new possibilities for identification of other AD susceptibility genes, as those encoding for the estrogen receptors (ERs). A total of 193 patients with sporadic late-onset AD, meeting the NINCDS-ADRDA criteria, and a total of 202 control subjects, age and education matched, were included in this study. PvuII and XbaI ERalpha and HhaI APOE gene polymorphisms were evaluated in genomic DNA by Polymerase Chain Reaction (PCR). The frequency of the various ERalpha genotypes by the combination of P, p and X, x was calculated for controls and AD patients stratified based on ApoE typing. When the two ERalpha gene polymorphisms were analyzed in combination, 7 genotypes were recognized, with a significantly increased prevalence of PPXX genotype in AD patients compared to controls (P = 0.0001). Risk of AD increased by a factor of 7.6 (CI [1.10-62.3]) in homozygous APOE-epsilon4 individuals with PPXX ERalpha genotype. These results are consistent with a segregation of PPXX ERalpha genotype with a higher risk of developing late-onset sporadic AD in the Italian population. The ERalpha gene appears to interact with the APOE-epsilon4 genotype in determining AD susceptibility.

Aged↗
PubMed1999

Gluthatione level is altered in lymphoblasts from patients with familial Alzheimer's disease.

Intracellular levels of glutathione (GSH), glutathione disulphide (GSSG), glutamic acid and gamma-glutamyl cysteine synthetase (gamma-GCS) were measured in lymphoblast lines from patients with familial and sporadic Alzheimer's disease (AD) and from age-matched controls. Lymphoblasts carrying presenilins (PS) and amyloid precursor protein (APP) genes mutations showed significantly decreased GSH content with respect to controls. Levels of GSSG and glutamic acid, as well as the activity of gamma-GCS were not significantly different in lymphoblasts carrying genes mutations as compared with control cells. These results indicate that even peripheral cells not involved in the neurodegenerative process of AD show altered GSH content when carrying PS and APP genes mutations. The provided data appear to be in accordance with the known alteration of GSH levels in central nervous system and strengthen the hypothesis of oxidative stress as an important, possibly crucial mechanism in the pathogenesis of AD.

Alzheimer Disease↗
PubMed1999

HLA A2 allele is associated with age at onset of Alzheimer's disease.

The prevalence of the HLA A2 allele was investigated in a group of Italian patients with sporadic and early-onset familial Alzheimer's disease (AD and FAD) to analyze the potential association of this allele with early age of onset of the disease. The possible interaction between the HLA A2 allele and apolipoprotein E epsilon4 allele was analyzed. Our data suggest that A2 and epsilon4 alleles may have additive effects on AD onset, and that A2 may play an important role in determining or contributing to a very early age at onset. These findings further support the hypothesis of the involvement of an immune/inflammatory mechanism in the pathogenesis of AD.

Adult↗
PubMed1999

Oxidative stress and a key metabolic enzyme in Alzheimer brains, cultured cells, and an animal model of chronic oxidative deficits.

Oxidative stress and diminished metabolism occur in several neurodegenerative disorders. Brains from Alzheimer's disease (AD) patients exhibit several indicators of oxidative stress and have reduced activities of the alpha-ketoglutarate dehydrogenase complex (KGDHC), a key mitochondrial enzyme. Whether these abnormalities are secondary to neurodegenerative processes or are inherent properties of the cells cannot be determined in autopsy brain. Studies in cultured fibroblasts suggest that AD-related differences in oxidative stress and KGDHC reflect inherent properties of AD cells. KGDHC is sensitive to oxidative stress whether the enzyme is studied in cells, in purified mitochondria, or as an isolated protein. Reductions of brain KGDHC in living rodents lead to oxidative stress and selective cell death. The results suggest that KGDHC participates in a deleterious cascade of events related to oxidative stress that are critical in selective neuronal loss in neurodegenerative diseases.

Alzheimer Disease↗
PubMed1998

Evidence for an Alzheimer disease susceptibility locus on chromosome 12 and for further locus heterogeneity.

CONTEXT: Alzheimer disease (AD) susceptibility genes have been identified on chromosomes 1, 14, 19, and 21, and a recent study has suggested a locus on chromosome 12. OBJECTIVE: To confirm or refute the existence of a familial AD susceptibility locus on chromosome 12 in an independent sample of familial AD cases. DESIGN: Retrospective cohort study. DNA data for 6 chromosome 12 genetic markers were evaluated using parametric lod score and nonparametric linkage methods and linkage heterogeneity tests. The latter include the admixture test of homogeneity in the total group of families and the predivided sample test in families stratified by the presence or absence of an apolipoprotein E (APOE) epsilon4 allele among affected members. Parametric analyses were repeated assuming autosomal dominant inheritance of AD and either age- and sex-dependent penetrance or zero penetrance for the analysis of unaffected relatives. SETTING: Clinical populations in the continental United States, Canada, Argentina, and Italy. PATIENTS: Fifty-three white families composed of multiple members affected with AD, from whom DNA samples were obtained from 173 patients with AD whose conditions were diagnosed using established criteria and from 146 nondemented relatives. MAIN OUTCOME MEASURE: Presence of an APOE epsilon4 allele among affected family members. RESULTS: Using parametric methods, no evidence for linkage to the region spanned by the chromosome 12 markers could be detected if familial AD is assumed to arise from the same genetic locus in all 53 families. However, significant evidence for linkage was detected in the presence of locus heterogeneity using the admixture test (odds ratio, 15, 135:1). The estimated proportion of linked families within the 53 families examined varied between 0.40 and 0.65, depending on the genetic model assumed and APOE status. The precise location of the AD gene could not be determined, but includes the entire region suggested previously. Nonparametric linkage analysis confirmed linkage to chromosome 12 with the strongest evidence at D12S96 (P<.001). CONCLUSIONS: Our data provide independent confirmation of the existence of an AD susceptibility locus on chromosome 12 and suggest the existence of AD susceptibility genes on other chromosomes. Screening a larger set of families with additional chromosome markers will be necessary for identifying the chromosome 12 AD gene.

Adult↗
PubMed1998

Absence of association between Alzheimer disease and the -491 regulatory region polymorphism of APOE.

A novel polymorphism (-491 A/T) within the regulatory region on the apolipoprotein E gene has recently been reported to be associated with risk for Alzheimer disease (AD). To test this association in an independent data set, we have examined this polymorphism in a sample of 88 well-characterized AD cases and compared the allele frequency and genotype frequencies for this polymorphism with those observed in 112 cognitively normal subjects drawn from the same ethnic group. These results suggest that in the current data set at least, the -491 A/T polymorphism is not associated with risk for AD, but may be in partial linkage disequilibrium with the APOE epsilon2/epsilon3/epsilon4 polymorphism.

Aged↗