Biomedical subjects

Sandra Schmitz

Publications and source records attributed to Sandra Schmitz.

6 recordsLinked to original sources

PubMed2004

Putative association of polymorphism in the mannose 6-phosphate receptor gene with major depression and Alzheimer's disease.

The endosomal lysosomal system might play a role in Alzheimer's disease, but its impact in major depression is unknown. The expression of the cation-dependent mannose 6-phosphate receptor (CD-MPR) is increased in Alzheimer's disease and the CD-MPR gene is located next to a region on chromosome 12 possibly linked to Alzheimer's disease. We investigated a C/T polymorphism in the CD-MPR gene in 188 Alzheimer's disease patients, in a control sample of 193 patients with major depression, as hospitalized controls, and in 259 healthy controls. We examined the interaction of the CD-MPR polymorphism with the putative risk factor for Alzheimer's disease, the cathepsin D T-allele. No significant association of the CD-MPR C-allele with Alzheimer's disease was observed. However, exploratory data analysis revealed an increased frequency of the CD-MPR C-allele in patients with major depression; thus, the C-allele may be a risk factor for depression. Gene location and function of the CD-MPR suggest an involvement in Alzheimer's disease; however, we could not find an association of the CD-MPR polymorphism with Alzheimer's disease. Since exploratory data suggest an involvement of the endosomal lysosomal system in major depression, further studies are warranted to investigate the biological role of the CD-MPR in major depression.

Aged↗

PubMed2003

Association of the C766T polymorphism of the low-density lipoprotein receptor-related protein gene with Alzheimer's disease.

The low-density lipoprotein receptor-related protein (LRP) is one of the most important cholesterol receptors in the brain. Gene variation of its ligand, apolipoprotein E, is a major genetic risk-factor for Alzheimer's disease (AD). The C-allele of the silent C766T polymorphism in exon 3 of the LRP gene might be associated with AD, however, results are conflicting and thus discussed controversially. Consequently, we compared the prevalence of this polymorphism in a homogenous cohort of patients with AD and control subjects. We found that carriers of a C-allele were at lower risk of AD; in agreement with this observation, AD patients who were carriers of a C-allele presented with a later age at onset of the disease than carriers of the TT genotype. These data suggest that LRP polymorphism influences the risk as well as the age at onset of AD. Our results contrast with other studies which described the C-allele to be a risk-factor for AD, but are in line with a recent publication on the effect of LRP polymorphism on longevity and on the risk for coronary artery disease. Further research on LRP polymorphisms is needed to evaluate their effects on the risk of AD, on coronary artery disease and on longevity.

Alzheimer Disease↗

PubMed2003

Investigation of a genetic variation of a variable number tandem repeat polymorphism of interleukin-6 gene in patients with multiple sclerosis.

Interleukin-6 (IL-6) plays an important role in the regulation of the inflammatory response in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Previous reports indicated that the C allele of a variable number tandem repeat (vntr) polymorphism located in the 3'flanking region of the IL-6 gene ( IL-6) is associated with reduced activity of IL-6 in vivo. Since disease-modifying genes are likely to contribute to phenotypic differences in MS patients, we tested the hypothesis that the IL-6 C allele is associated with the clinical course of MS. The IL-6 C allele was equally distributed between 217 MS patients of German Caucasian origin and 111 age-mached healthy controls. Stratification of patients according to the course of disease revealed no significant difference of IL-6 C allele distribution between patients with primary progressive and those with either relapsing-remitting or secondary progressive MS although IL-6 C allele was more frequent in patients with RR-MS. Since IL-6 C allele has been associated with a benign course in Sardinian MS patients, we further analysed an independent sample of 125 Sardinian MS patients revealing that IL-6 C allele was much more frequent than in German MS patients. Taken together, a disease-modifying effect of IL-6 C allele could not be demonstrated in MS patients of German Caucasian descent.

Adult↗

PubMed2003

Association of an interleukin-1beta gene polymorphism at position -511 with Alzheimer's disease.

Inflammation is thought to promote neuronal cell death in Alzheimer's disease (AD). The proinflammatory interleukin-1 is a main component in inflammatory pathways and is overexpressed in the brain of AD patients. Investigation of different polymorphisms in the interleukin-1 genes (IL-1alpha -889, IL-1beta -511, IL-1beta +3953) revealed associations between specific alleles and AD in that they increased the risk or modified the age at onset of AD. However, there are controversial findings from other studies which revealed no significant associations between these polymorphisms and AD; thus further evaluation of the association of IL-1 gene polymorphisms with AD and their role in pathogenesis is needed. In this study we examined the distribution of the IL-1beta -511 alleles in AD patients and a control sample of healthy individuals. An additional control population of non-demented depressive inpatients was recruited to exclude a confounding bias. The cerebrospinal fluid (CSF) levels of Abeta42 in AD patients were investigated to assess the influence of IL-1beta -511 genotypes. We found no significant association of the IL-1beta -511 polymorphism with AD, suggesting that the IL-1beta -511 polymorphism is no risk factor for AD. However, we found the Abeta42 CSF levels to be lower in carriers of the IL-1beta CC-genotype compared to carriers of the T-allele. Even though IL-1beta -511 polymorphism did not influence the risk of AD it might have a pathophysiological influence on the disease process.

Aged↗

PubMed2002

Spatial direction of attention enhances right hemispheric event-related gamma-band synchronization in humans.

Gamma-band oscillations are related to sensory information processing and attention. To further illuminate the relationship of gamma-band activity and selective somatic attention, we have studied the effects of direction of attention on the stimuli of somatosensory evoked potentials. Responses during focused attention to stimulation of the right median nerve and ignored stimulation at the right tibial nerve were compared with responses of ignored stimulation of the right median nerve but focused attention to stimulation at the right tibial nerve. Subtraction of the data demonstrated a significant predominantly right hemispheric event-related synchronization in the gamma-band by attention to the right median nerve in the time period between 280 and 325 ms post-stimulus. This finding implicates the involvement of a right temporoparietal network in selective spatial attention.

Adult↗

PubMed2002

Cathepsin D: screening for new polymorphisms using single-strand conformation polymorphism analysis.

Cathepsin D (CTSD) is a lysosomal protease involved in the pathogenesis of several diseases such as breast cancer and possibly Alzheimer's disease (AD). Previous findings revealed a significant association between the T allele of the 224 C/T (A58V) polymorphism in exon 2 of the CTSD gene and late onset AD. The exonic regions of the CTSD gene were screened for further polymorphic variations using polymerase chain reaction and single-strand conformation polymorphism analysis. In addition to the known 224 C/T polymorphism and two silent mutations in exons 3 and 4 we detected two new polymorphisms in introns 5 and 8. Combination of these sequence variations results in three different haplotypes; one of these haplotypes is due to the new polymorphism in intron 5. We detected no further missense mutations except for the known 224 C/T polymorphism in exon 2. Thus, if sequence variations within the CTSD gene influence the risk for various diseases, the pathogenic mechanism is likely to be linked to the amino acid substitution in the profragment of CTSD.

Adult↗