Alzheimer Disease: Boda K

Kálmán J, Palotás A, Kis G, Boda K, Túri P, Bari F, Domoki F, Dóda I, Argyelán M, Vincze G, Séra T, Csernay L, Janka Z, Pávics L. · Albert Szent-Györgyi Medical and Pharmaceutical Center, Faculty of Medicine, University of Szeged, H-6721 Szeged, Semmelweis u. 6, Hungary. · Eur J Neurosci. · Pubmed #15845094 No free full text.

Abstract: Bilateral temporoparietal hypoperfusion is a characteristic single photon emission computed tomography (SPECT) finding in Alzheimer's disease (AD). Lactate is a metabolic vasodilator and is known to provoke increased cerebral blood flow (CBF) in healthy adults. This work investigated whether lactate, which is present in high concentrations in AD cerebrospinal fluid, affects AD-specific perfusion abnormalities. Twenty mild-to-moderately demented AD probands participated in the self-controlled study. The regional CBF was examined utilizing (99m)Tc-HMPAO SPECT after sodium lactate infusion (0.5 M, 5 mL/kg body weight) and 0.9% NaCl infusion, one on each of two separate days. Despite the vasodilatator effects of sodium lactate, AD rCBF patterns did not show increase in temporo-parietal regions after its infusion. AD-specific bi-temporo-parietal reduction in CBF was accompanied by further hypoperfusion in the parieto-occipital areas after the sodium lactate infusion in seven patients, while no CBF changes were observed in the case of the remaining 13 probands. The pattern of the CBF abnormalities was not correlated with the apolipoprotein E genotype. The decreased vascular responsiveness to sodium lactate reflects disturbed vasoregulatory processes in AD and it is unlikely that lactate would have any relevance in the treatment of AD-related cerebral hypoperfusion, but could be used to improve the value of perfusion SPECT in the diagnosis of AD.

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.

Zana M, Szécsényi A, Czibula A, Bjelik A, Juhász A, Rimanóczy A, Szabó K, Vetró A, Szucs P, Várkonyi A, Pákáski M, Boda K, Raskó I, Janka Z, Kálmán J. · Department of Psychiatry, Alzheimer's Disease Research Center, Faculty of Medicine, Albert Szent-Györgyi Center for Medical and Pharmaceutical Sciences, University of Szeged, 6 Semmelweis St., Szeged, H-6725, Hungary. · Biochem Biophys Res Commun. · Pubmed #16696946 No free full text.

Abstract: The aim of the present study was to investigate the oxidative status of lymphocytes from children (n=7) and adults (n=18) with Down's syndrome (DS). The basal oxidative condition, the vulnerability to in vitro hydrogen peroxide exposure, and the repair capacity were measured by means of the damage-specific alkaline comet assay. Significantly and age-independently elevated numbers of single strand breaks and oxidized bases (pyrimidines and purines) were found in the nuclear DNA of the lymphocytes in the DS group in the basal condition. These results may support the role of an increased level of endogenous oxidative stress in DS and are similar to those previously demonstrated in Alzheimer's disease. In the in vitro oxidative stress-induced state, a markedly higher extent of DNA damage was observed in DS children as compared with age- and gender-matched healthy controls, suggesting that young trisomic lymphocytes are more sensitive to oxidative stress than normal ones. However, the repair ability itself was not found to be deteriorated in either DS children or DS adults.

Juhász A, Rimanóczy A, Boda K, Vincze G, Szlávik G, Zana M, Bjelik A, Pákáski M, Bódi N, Palotás A, Janka Z, Kálmán J. · Department of Psychiatry, Albert Szent-Györgyi Medical and Pharmaceutical Center, Faculty of Medicine, University of Szeged, Szeged, Hungary. · Neurochem Res. · Pubmed #16258842 No free full text.

Abstract: Multiple genetic and environmental factors regulate the susceptibility to Alzheimer's disease (AD). Recently, several independent studies have reported that a locus on chromosome 14q32.1, where a gene encoding a cholesterol degrading enzyme of the brain, called 24-hydroxylase (CYP46A1) is located, has been linked with AD. The single nucleotide polymorphism (T/C) in intron 2 of CYP46 gene has been found to confer the risk for AD. The water soluble 24(S)-hydroxysterol is the product of the CYP46A1, and elevated plasma and cerebrospinal fluid hydroxysterol concentrations have been found in AD, reflecting increased brain cholesterol turnover or cellular degradation, due to the neurodegenerative process. A case-control study was performed on 125 AD and 102 age- and gender-matched control subjects (CNT) from Hungary, to test the association of CYP46 T/C and apolipoprotein E (ApoE) gene polymorphisms in AD. The frequency of the CYP46 C allele was similar (chi2=0.647, df=1, P=0.421, exact P=0.466, OR=0.845; 95% CI: 0.561-1.274) in both groups (CNT: 27%; 95% CI: 21.3-33.4; AD 30%; 95% CI: 25.0-36.3). The ApoE varepsilon4 allele was significantly over-represented (chi2=11.029, df=2, P=0.004) in the AD population (23.2%; 95% CI: 18.2-29.0) when compared with the CNT (11.3%; 95% CI: 7.4-16.6). The presence or absence of one or two CYP46C alleles together with the ApoE varepsilon4 allele did not increase the risk of AD (OR=3.492; 95% CI: 1.401-8.707; P<0.007 and OR=3.714; 95% CI: 1.549-8.908; P<0.003, respectively). Our results indicate that the intron 2 T/C polymorphism of CYP46 gene (neither alone, nor together with the varepsilon4 allele) does not increase the susceptibility to late-onset sporadic AD in the Hungarian population.

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.

Zana M, Juhász A, Rimanóczy A, Bjelik A, Baltás E, Ocsovszki I, Boda K, Penke B, Dobozy A, Kemény L, Janka Z, Kálmán J. · Department of Psychiatry, Albert Szent-Györgyi Center for Medical and Pharmaceutical Sciences, University of Szeged, 6 Semmelweis Street, Szeged H-6725, Hungary. · Neurobiol Aging. · Pubmed #15961188 No free full text.

Abstract: In the present pilot investigation, the susceptibility of T-lymphocytes from Alzheimer's disease (AD) subjects (n=22) and aged-matched, non-demented controls (CNT) (n=12) was examined with ultraviolet (UV) B light-induced apoptosis in vitro. The basal apoptotic ratios were similar in both groups. However, the AD lymphocytes displayed significantly (p<0.0001) lower apoptotic levels than those of the CNT lymphocytes at all of the applied UVB exposure doses (100, 200 and 300 mJ/cm(2)). These observations indicate that AD lymphocytes are more resistant than CNT lymphocytes to UVB irradiation.

Boda K, Kálmán J, Janka Z. · Department of Medical Informatics, University of Szeged, Hungary. · Stud Health Technol Inform. · Pubmed #15460732 No free full text.

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Kálmán J, Juhász A, Janka Z, Rakonczay Z, Abrahám G, Boda K, Farkas T, Penke B. · No affiliation provided · Atherosclerosis. · Pubmed #15177135 No free full text.

This publication has no abstract.

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.

Kálmán J, Boda K, Bende Z, Janka Z. · Szegedi Tudományegyetem, Altalános Orvostudományi Kar, Szent Györgyi Albert Orvos- és Gyógyszerésztudományi Centrum, Pszichiátriai Klinika. · Orv Hetil. · Pubmed #14598572 No free full text.

Abstract: INTRODUCTION: The screening and recognition of dementing disorders are considered as important tasks of general practitioners. Despite of the recent progress made in the treatment of cognitive, behavioral symptoms and slowing down the rate of progression, difficulties are still existing in the early detection, and the most frequent dementia forms such as Alzheimer's disease (AD) and vascular dementia (VD) are underdiagnosed in Hungary. Any rapid, easy-to-use dementia screening method therefore could be of great value in the community. AIMS: The Hungarian standardisation of a new dementia screening tool, the 7 Minute Test (7MT) has been reported here. Accuracy, sensitivity and specificity were calculated. The authors provide new data regarding the discriminative power of this test in a variety of dementing and dementia related conditions. METHODS: The test results of 339 probands, referred to the local memory clinic, were evaluated in all subtests, where orientation in time, memory, verbal fluency, and visuoconstructive skills are assessed. The patients were clustered into seven groups according to their clinical diagnosis, such as: Control (CNT), Mild Cognitive Impairment (MCI), AD, VD, mixed AD-VD, depression (D) and Organic Amnestic Syndrome (OAS). RESULTS: In overall, the test successfully discriminated 77% of the CNT and all disease cases (sensitivity 85%, specificity 55%). When the AD and CNT groups were compared separately, the highest values: 91% sensitivity, 86% specificity have been found. A total score of 139 has been suggested as a cutoff value to separate CNT and dementia cases. These results suggest that the test is suitable to classify CNT and "real" dementia cases (AD, VD, mixed AD-VD), but not valid within the real dementia groups. Furthermore, it is not helpful for the identification of MCI, pseudodementia cases (D) and OAS as well. CONCLUSION: The 7MT could be a valuable dementia screening tool in the primary care, but it is not specific for any form of dementia.

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.

Janka Z, Juhász A, Rimanóczy A A, Boda K, Márki-Zay J, Kálmán J. · 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. · Mol Psychiatry. · Pubmed #11803456 links to  free full text

Abstract: The gene of an esterase enzyme, called paraoxonase (PON, EC.3.1.8.1.) is a member of a multigene family that comprises three related genes PON1, PON2, and PON3 with structural homology clustering on the chromosome 7.(1,2) The PON1 activity and the polymorphism of the PON1 and PON2 genes have been found to be associated with risk of cardiovascular diseases such as hypercholesterolaemia, non-insulin-dependent diabetes, coronary heart disease (CHD) and myocardial infaction.(3-8) The importance of cardiovascular risk factors in the pathomechanism of Alzheimer's disease (AD) and vascular dementia (VD)(9-13) prompted us to examine the genetic effect of PON2 gene codon 311 (Cys-->Ser; PON2*S) polymorphism and the relationship between the PON2*S allele and the other dementia risk factor, the apoE polymorphism in these dementias. The PON2*C and PON2*S allele frequencies were similar in both AD (25% and 75%) and VD groups (23% and 77%), respectively, compared with the controls (27% and 73%). The ratio of the PON2*S carriers was significantly higher among the apoE4 allele carrier AD (27%) and VD (25%) groups than in the control (12%). Our results indicate that the PON2*S and apoE4 alleles have interactive effect on the development of the two most common forms of dementias AD and VD, and further support the hypothesis that cardiovascular factors contribute to the development of AD.

Engelhardt JI, Le WD, Siklós L, Obál I, Boda K, Appel SH. · Department of Neurology, Baylor College of Medicine, Houston, Tex 77030, USA. · Arch Neurol. · Pubmed #10815134 links to  free full text

Abstract: CONTEXT: The participation of an immune/inflammatory process in the pathomechanism of sporadic Alzheimer disease (AD) has been suggested by evidence for activated microglia and the potential therapeutic benefit of anti-inflammatory medication. OBJECTIVE: To define a possible role for IgG in the immune/inflammatory process of AD in humans, we assayed the ability of IgG samples from patients with AD to target the injury to cholinergic neurons in rat basal forebrain in vivo. DESIGN: IgG purified from the serum or plasma from patients with AD and patients with other neurological disease who were used as control (DC) patients was injected stereotaxically into the medial septum of adult rats. Four weeks later coronal sections of the whole medial septum-diagonal bands of Broca region were immunostained for choline acetyltransferase (ChAT) to identify cholinergic neuronal cells. SETTING: University medical centers. PATIENTS: Blood samples were collected from 8 patients with probable and definite AD and from 6 age-matched DC patients. MAIN OUTCOME MEASURE: Detection of changes in the number of ChAT immunopositive cell profiles in sections and statistical evaluation. RESULTS: Four weeks after the injections, IgG samples from patients with AD significantly reduced the number of ChAT-immunostained cell profiles in the whole medial septum-diagonal bands of Broca region compared with IgGs from DC patients. Neither DC IgGs nor saline solution significantly decreased the number of ChAT-immunopositive neuronal cell profiles. CONCLUSION: Data document that IgG from patients with AD can target a stereotaxically induced immune/inflammatory injury to cholinergic neurons in the rat basal forebrain in vivo.