Alzheimer Disease: Palotás M

Kálmán J, Juhász A, Rimanóczy A, Palotás A, Palotás M, Szabó Z, Boda K, Márki-Zay J, Janka Z. · Department of Psychiatry, Albert Szent-Györgyi Center for Medical and Pharmaceutical Sciences, Faculty of Medicine, University of Szeged, Semmelweis u.6, H-6725 Szeged, Hungary. · Dement Geriatr Cogn Disord. · Pubmed #12714797 No free full text.

Abstract: The objective of our study was to investigate whether an interaction exists between apolipoprotein E (APOE) genotype and the response of patients with Alzheimer's disease (AD) to selegiline treatment, and whether APOE genotype independently affects the rate of AD progression. A 48-week multicenter double-blind trial was undertaken on 43 patients with mild to moderate AD. Primary efficacy measures were the AD Assessment Scale (ADAS), an 11-item cognitive subscale of ADAS (ADAS-Cog/11) and the Mini Mental State Examination. Secondary outcome measures were Clinical Global Impression of severity and CGI of change scales. The therapeutic response to selegiline was not affected by APOE genotype. Our results revealed that the APOE4 allele carrier AD probands did not respond better to selegiline treatment than the APOE2-3 patients, i.e. APOE status did not influence the therapeutic outcome of selegiline treatment.

Kálmán J, Palotás M, Pákáski M, Hugyecz M, Janka Z, Palotás A. · University of Szeged, Department of Psychiatry, Hungary. · Eur J Anaesthesiol. · Pubmed #16884554 No free full text.

Abstract: BACKGROUND AND OBJECTIVE: Recent studies emphasize a positive correlation between (cardiac) surgical interventions and increased risk for developing Alzheimer's disease in the late postoperative period. Since amyloid precursor protein and its neurotoxic derivatives play key roles in the development of Alzheimer's dementia, the impact of several agents used in the intra- and perioperative period is examined. METHOD: Amyloid precursor protein concentrations were assessed by semi-quantitative Western-immunoblot in brains of rats following intraperitoneal treatment with diazepam and midazolam. RESULTS: There were no significant changes in the amyloid precursor protein concentrations. CONCLUSION: Both diazepam and midazolam are considered to be relatively safe with respect to amyloid precursor protein metabolism.

Palotás M, Palotás A, Bjelik A, Pákáski M, Hugyecz M, Janka Z, Kálmán J. · Department of Psychiatry, Albert Szent-Györgyi Medical and Pharmaceutical Center, Faculty of Medicine, University of Szeged, H-6721, Szeged, Semmelweis u. 6, Hungary. · Neurochem Res. · Pubmed #16258851 No free full text.

Abstract: The incidence of Alzheimer's disease is elevated after exposure to surgical interventions. Since amyloid precursor protein (APP) and its neurotoxic derivatives play key roles in the development of Alzheimer dementia, the role of general anesthesia is controversial in the development of cognitive decline. As such, the effect of anesthetics on APP protein and mRNA levels was assessed utilizing semiquantitative Western-immunoblot and reverse transcription polymerase chain reaction (RT-PCR) in brains of rats following intraperitoneal treatment with propofol and thiopental. The anesthetics did not change cortical APP protein and mRNA concentration considerably. These results indicate that both propofol and thiopental are considered to be relatively safe with respect to APP metabolism.

Juhász A, Palotás A, Janka Z, Rimanóczy A, Palotás M, Bódi N, Boda K, Zana M, Vincze G, Kálmán J. · Department of Psychiatry, Albert Szent-Györgyi Medical and Pharmaceutical Center, Faculty of Medicine, University of Szeged, Semmelweis u 6, H-6721, Szeged, Hungary. · Neurochem Res. · Pubmed #16176061 No free full text.

Abstract: Apolipoprotein E gene (Apo(epsilon)) has three common alleles (epsilon2, epsilon3, and epsilon4), of which epsilon4 has been shown to be associated with an increased risk for Alzheimer's disease (AD). Possible additional genetic factors, like the -491A variant of ApoE promoter may modify the development of AD, independently of the ApoE allele status. The objective of this study was to investigate whether A/T allelic polymorphism at site-491 of the ApoE promoter is associated with AD in a Hungarian population. The genomic DNA isolated from peripheral blood lymphocytes of 52 late-onset AD and 53 control individuals was used as a template for the two examined polymorphisms and PCR assay was applied. The epsilon4 allele was significantly over-represented in the AD group (28%) as compared with the control population (7%). No significant differences have been found between the control and the AD populations regarding the occurrence of the promoter A allele frequencies (control: 77%, AD: 70%). However, the AA genotype was more frequent in the AD group (48%) than in the control (10%) when the presence of epsilon4 allele was also considered. It is unlikely therefore that the -491A variant of the ApoE promoter gene is an independent risk factor in the Hungarian AD population, but a linkage disequilibrium exists between the two examined mutations.

Palotás A, Puskás LG, Kitajka K, Palotás M, Molnár J, Pákáski M, Janka Z, Penke B, Kálmán J. · Department of Psychiatry, Albert Szent-Györgyi Medical and Pharmaceutical Center, Faculty of Medicine, University of Szeged, H-6721 Szeged, Semmelweis u. 6, Hungary. · Eur J Pharmacol. · Pubmed #15336942 No free full text.

Abstract: Antidepressants are widely used in the treatment of mood disorders associated with dementia, however little information is available on their effect at the molecular level. We have demonstrated that gene expression profiles of lymphocytes from patients with Alzheimer dementia differ from that seen with controls, with alpha(2)-adrenoceptor being the most highly repressed transcript. To address this issue in light of antidepressant treatment, we used lymphocytes derived from Alzheimer patients and control individuals to assess the impact of mirtazapine, the novel antidepressant with alpha(2)-adrenoceptor antagonistic activities, on gene expression using a cDNA microarray representing 3200 distinct human genes. Sequences that are differentially regulated after treatment with mirtazapine were identified and categorized based on similarities in biological functions. This analysis revealed that selected biological processes, including protein metabolism, cytoskeleton integrity, immune response, cellular plasticity, and neurotransmission, are involved in early phases of administration of this antidepressant. In addition, although it was possible to identify common targets, the expression profiles of Alzheimer lymphocytes differed mainly in their magnitude from those seen with controls. These results confirm the usefulness of the gene array approach for studying Alzheimer-specific changes in the periphery and suggest that the expression of genes of Alzheimer lymphocytes is modulated differently by mirtazapine, which correlates with the pathology.

Palotás A, Puskás LG, Kitajka K, Palotás M, Molnár J, Pákáski M, Janka Z, Penke B, Kálmán J. · Department of Psychiatry, Albert Szent-Györgyi Medical and Pharmaceutical Center, Faculty of Medicine, University of Szeged, H-6721 Szeged, Hungary. · Neurochem Res. · Pubmed #15260135 No free full text.

Abstract: Antidepressants are widely used in the treatment of mood disorders associated with dementia, however little information is available on their effect at the molecular level. In certain neurodegenerative disorders, such as in Alzheimer's disease, lymphocytes have been used to assess mirror changes that thought to occur in the brain. Gene expression profiles of lymphocytes from Alzheimer patients have been shown to differ from that seen with controls. To address this issue in light of antidepressant treatment, we used lymphocytes derived from Alzheimer's disease patients and control individuals to assess the impact of the selective serotonine reuptake inhibitor citalopram on gene expression using a cDNA microarray representing 3200 distinct human genes. Sequences that are differentially regulated after treatment with citalopram were identified and categorized based on similarities in biological functions. This analysis revealed that the overexpression of genes in control and Alzheimer white blood cells by citalopram are implicated in cell survival. Apart from this, citalopram did not markedly alter genes involved in other molecular functions in control cells. In contrast, alteration of genes implicated in ionic currents, cell-adhesion, immune mechanism, and adrenergic functions, were also observed in Alzheimer lymphocytes. The expression of genes of Alzheimer lymphocytes by citalopram is modulated differently which may correlate with the pathology.

Palotás A, Penke B, Palotás M, Kenderessy AS, Kemény L, Kis E, Vincze G, Janka Z, Kálmán J. · Department of Medical Chemistry, University of Szeged, Szeged, Hungary. · Skin Pharmacol Physiol. · Pubmed #15258451 No free full text.

Abstract: BACKGROUND: Antipsychotics are widely used in the treatment of behavioral and psychological symptoms of dementia. A low frequency of Alzheimer's disease in patients with schizophrenia is reported, and it has been proposed that antipsychotic medications, such as haloperidol, may be responsible. Disruption of intracellular calcium levels is considered to play a key role in beta-amyloid-induced neurotoxicity in Alzheimer's disease. Haloperidol has also been reported to interact with calcium homeostasis through dopamine-2 and sigma-1 receptors, and other, yet unknown mechanisms. OBJECTIVE: Therefore, we investigated whether differences in the basal intracellular free calcium levels of cultured cutaneous fibroblasts--cells that do not express dopamine-2 and sigma-1 receptors--derived from sporadic Alzheimer patients and from age-matched control individuals after haloperidol treatment might be present. METHODS: Intracellular calcium level was measured in Fura-2AM-loaded human fibroblasts by dual wavelength spectrofluorimetry. RESULTS: Alzheimer cells exhibited significantly lower calcium level as compared to the control cultures. Exposure of fibroblasts to beta-amyloid peptide resulted in increased calcium concentration of the control cells, but not of Alzheimer fibroblasts. Co-incubation of cultures with a therapeutic dose of haloperidol blocked the beta-amyloid-induced elevation of calcium. CONCLUSION: This finding indicates that haloperidol efficiently countervails ionic imbalance and suggests that it may serve as a potential agent in alleviating neurotoxic effects of beta-amyloid peptide.

Kálmán J, Juhász A, Rimanóczy A, Palotás A, Palotás M, Boda K, Márki-Zay J, Csibri E, Janka Z. · Department of Psychiatry, Albert Szent-Györgyi Center for Medical and Pharmaceutical Sciences, Faculty of Medicine, University of Szeged, Hungary. · Psychiatr Genet. · Pubmed #14639046 No free full text.

Abstract: An association study was performed between apolipoprotein E (apoE) polymorphism and the common structural polymorphism Glu/Asp at codon 298 of the nitric oxide synthase (NOS3) gene in late-onset sporadic Alzheimer's dementia probands (LOAD), diffuse Lewy body dementia cases (DLBD) and controls in a Hungarian sample. The frequency of individuals who carried the apoE epsilon4 allele was significantly more common in both dementia groups (LOAD, 20%; DLBD, 27%; control, 8%; control versus DLBD, chi2=13.264, degrees of freedom=2, P<0.001; control versus LOAD, chi2=6.628, degrees of freedom=2, P<0.036). However, there were no significant differences in the NOS3 genotype and allele distributions between the LOAD, DLBD and control groups. The apoE status has been found to be independent from the NOS3 codon 298 polymorphism in the examined cohort. Despite the facts that NOS3 is associated with neuritic sprouting, and aberrant neuronal and glial expression of the same molecule has been found in neurodegenerative diseases, it is unlikely that the polymorphism Glu/Asp of the NOS3 gene is involved in the development of LOAD and DLBD.

Palotás A, Kálmán J, Palotás M, Matin K, Szentpáli K, Paszt A, Janka Z, Penke B. · Department of Medical Chemistry, University of Szeged, H-6721 Szeged, Dóm tér 8, Hungary. · Neurochem Res. · Pubmed #12515309 No free full text.

Abstract: Beta-amyloid peptide plays a crucial role in the pathology of Alzheimer's disease. As part of our ongoing fluorimetric studies, in the present report we demonstrate differences in resting intracellular free calcium levels of cells in the blood derived from sporadic Alzheimer patients and from age-matched control individuals. Calcium levels were measured in Fura-2AM-loaded human blood samples by dual-wavelength spectrofluorimetry. The resting calcium concentrations of blood samples from Alzheimer patients were lower compared to that of the control samples. Exposure of control blood samples to beta-amyloid caused an increase in the calcium level. Specimens from Alzheimer donors, however, appeared to be resistant to the peptide. This simple finding may serve as a springboard to monitoring Alzheimer pathology in the peripheral systems of the body.

Palotás A, Kálmán J, Palotás M, Juhász A, Janka Z, Penke B. · Department of Medical Chemistry, University of Szeged, Szeged, Hungary. · Prog Neuropsychopharmacol Biol Psychiatry. · Pubmed #12369273 No free full text.

Abstract: A major neuropathological finding in Alzheimer's disease (AD) is the presence of senile plaques in certain regions in the brain. The plaques contain extracellular deposits of beta-amyloid peptide (beta AP). Destabilization of intracellular calcium homeostasis in neurons, caused by beta AP, plays a central role in AD pathogenesis. In the present study, the authors report ionic alterations of lymphocytes and fibroblasts harvested from sporadic AD patients and from age-matched controls. Intracellular free calcium level ([Ca2+]i) of human cells, labeled with Fura-2AM, was determined by dual wavelength spectrofluorimetry. Basal [Ca2+]i appeared to be higher in AD lymphocytes when compared to control ones. Resting [Ca2+]i of AD fibroblasts, however, has proven to be lower than that seen with control cells. Exposure of cells to beta AP resulted in the elevation of the [Ca2+]i in both control cell types, however, that of AD lymphocytes and fibroblasts did not differ considerably.

Palotás A, Kálmán J, Palotás M, Juhász A, Janka Z, Penke B. · Department of Medical Chemistry, University of Szeged, Szeged, Hungary. · Brain Res Bull. · Pubmed #12127018 No free full text.

Abstract: Senile plaques containing beta-amyloid peptide (betaAP) comprise the major neuropathological lesions in Alzheimer's disease (AD). In line with ongoing studies investigating alterations of various biochemical processes of cells of peripheral tissues, the authors demonstrate differences in resting intracellular free calcium levels of lymphocytes harvested from sporadic Alzheimer patients and from age-matched controls. Resting intracellular calcium concentration was measured in Fura-2AM-loaded human lymphocytes by dual wavelength spectrofluorimetry. Resting calcium level appeared to be higher in Alzheimer cells when compared to control lymphocytes. After incubating cells in 10(-7)M of beta-amyloid, the resting calcium concentration of the control cells elevated, while that of Alzheimer lymphocytes did not differ considerably.

Janka Z, Juhász A, Rimanóczy A, Boda K, Márki-Zay J, Palotás M, Kuk I, Zöllei M, Jakab K, Kálmán J. · Department of Psychiatry, Albert Szent-Györgyi Center for Medical and Pharmaceutical Sciences, Faculty of Medicine, University of Szeged, Szeged, Hungary. · Psychiatr Genet. · Pubmed #11901360 No free full text.

Abstract: Several lines of biochemical evidence support a role of alpha2-macroglobulin (A2M) in the pathogenesis of Alzheimer's dementia (AD). A2M participates in the general defence mechanism against proteinases and it is supposed to be involved in the degradation of beta-amyloid peptide (betaAP). Furthermore, A2M has been shown to reduce betaAP fibril formation, and it is upregulated in the acute-phase inflammatory response like the process occurring in the AD brain. The exon 18 splice acceptor deletion polymorphism and the exon 24 (Val-1000-Ile) GG genotype were reported to be associated with AD, but the results are contradictory. Since the Hungarian population is genetically distinct from the other European ethnic groups, we examined whether the risk for developing AD is increased in the A2M GG carriers. The interaction of apolipoprotein E (apoE) and A2M polymorphisms was also examined. The distribution of A2M genotypes and alleles in the entire data set was consistent with the previous negative observations in which A and G allelic frequencies were comparable in both groups (72% and 28% in the AD population, and 72% and 28% in the control population, respectively). The GG genotype was over-represented (14%) only in the apoE epsilon4 non-carrier subgroup of AD probands (7% in the control group), but the difference was not significant. Our data suggest that, although A2M has an important role in the AD-specific neurodegenerative process, its exon 24 Val-1000-Ile polymorphism is not likely to be associated with late-onset sporadic AD in the Hungarian population.