Alzheimer Disease: Palotás A

Baranov D, Bickler PE, Crosby GJ, Culley DJ, Eckenhoff MF, Eckenhoff RG, Hogan KJ, Jevtovic-Todorovic V, Palotás A, Perouansky M, Planel E, Silverstein JH, Wei H, Whittington RA, Xie Z, Zuo Z, Anonymous00067. · Department of Anesthesiology and Critical Care, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA. · Anesth Analg. · Pubmed #19372347 No free full text.

Abstract: In order to review the current status of the potential relationship between anesthesia and Alzheimer's disease, a group of scientists recently met in Philadelphia for a full day of presentations and discussions. This special article represents a consensus view on the possible link between Alzheimer's disease and anesthesia and the steps required to test this more definitively.

Palotás A, Kálmán J. · Alzheimer's Disease Research Center, Department of Psychiatry, Albert Szent-Györgyi Medical and Pharmaceutical Center, Faculty of Medicine, University of Szeged, H-6720 Szeged, Pécsi u. 4, Hungary. · Curr Drug Metab. · Pubmed #16611022 No free full text.

Abstract: Alzheimer's disease (AD) is a genetically complex and heterogenous disorder. In a small proportion of cases, mutations in three determinative (causal) genes are responsible for autosomal dominant early-onset forms of AD. The majority of cases, however, is sporadic, late-onset AD with unknown etiology. The pathology and clinical manifestations of these forms are influenced by multiple genetic and environmental risk factors. Over the past decades, a number of candidate genes have been identified as disease modifiers with conflicting results. This study reviews susceptibility genes that are associated with increased risk of developing AD.

Kálmán J, Palotás A, Bódi N, Kincses TZ, Benedek G, Janka Z, Antal A. · Department of Psychiatry, Albert Szent-Györgyi Medical and Pharmaceutical Center, Faculty of Medicine, University of Szeged, H-6721 Szeged, Semmelweis u. 6, Hungary. · Brain Res Bull. · Pubmed #15862926 No free full text.

Abstract: Impaired neuronal energy metabolism, oxidative changes and microvascular abnormalities lead to altered lactate levels in Alzheimer's dementia. The aim of the present study was to assess whether intravenous sodium-lactate, a metabolic alternative and vasodilator that is thought to improve cognition, advances the cognitive performance of Alzheimer patients. Semantic categorization paradigm was used to present the electrophysiological correlates of natural scene categorization of Alzheimer patients before and after intravenous saline or sodium-lactate infusion. Mean amplitudes of event-related potentials (ERPs) were measured in two time windows before and after the treatments; two negative components (N1 between 150 and 250 ms and N2 between 400 and 600 ms) and one positive component (P2 between 250 and 400 ms) were identified. The negative components were more negative for the non-animal trials than for the animal trials while the positive component was similar for both categories. After the lactate treatment the amplitudes of the negative components became more negative mainly for the non-animal trials while the amplitude of the positive component turned more positive for the animal trials, however these changes were not significant. No changes have been observed after normal saline infusion. These results suggest that, contrary to its anticipated beneficial effects, sodium-lactate fails to significantly improve semantic categorization processes in Alzheimer's disease and this enhancement can be detected by recording ERPs. The effect of sodium-lactate to slightly improve semantic memory might be based on its positive effect on cardio- and cerebro-vascular function and neuronal metabolism.

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.

Mukhamedyarov MA, Grishin SN, Yusupova ER, Zefirov AL, Palotás A. · Department of Physiology, Kazan State Medical University, Kazan, Russia. · Cell Physiol Biochem. · Pubmed #19255505 No free full text.

Abstract: Numerous findings obtained over the last decades suggest that accumulation of beta-amyloid peptide (betaAP) plays the central role in the pathogenesis of Alzheimer's disease. It is well established that betaAP has wide range of toxic effects on neurons in vitro and in vivo, however the influence of betaAP in the periphery and on various other types of excitable tissues, eg. skeletal muscle cells, is almost unknown despite the many non-cognitive and other extra-neuronal symptoms associated with Alzheimer's dementia. Here we utilized conventional electrophysiological technique to investigate the effects and mechanisms of betaAP action on the resting membrane potential of frog skeletal muscle fibers. betaAP in the range of concentrations from 10(-6) to 10(-8)M produced slow, significant, reversible depolarization of muscle fiber membranes. The impact developed and was washed out faster at higher concentrations of betaAP (10(-6)-0(-7)M). The effect of betaAP was completely absent when applied in Na+-free Tris+ solutions. betaAP-mediated depolarization was also prevented by tetrodotoxin (10(-5)M) pre-treatment and rescued by tetrodotoxin after-treatment. These findings suggest that betaAP-induced depolarization of skeletal muscle plasma membranes can significantly disturb the functioning of skeletal muscles and therefore contribute to motor dysfunction observed in Alzheimer's disease and other disorders associated with betaAP accumulation.

Palotás A. · Asklepios-Med Bt., H-6722 Szeged, Kossuth Lajos sgt. 23, Szeged, Hungary. · Pharmacogenomics J. · Pubmed #17325731 No free full text.

This publication has no abstract.

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, 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.

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.

Palotás A, Kálmán J, Laskay G, Juhász A, Janka Z, Penke B. · Szegedi Tudományegyetem, Orvosi Vegytani Intézet, 6721 Szeged. · Ideggyogy Sz. · Pubmed #12122875 No free full text.

Abstract: RATIONALE: beta-amyloid peptides, comprising the major neuropathological lesions of Alzheimer's disease, have been found to form depositions in various peripheral tissues, including the skin. Neurons in the disorder succumb to the altered ionic homeostasis and some other factors caused by this toxic peptide. In line with these findings, our study aimed to find differences in biochemical processes of cultured cutaneous fibroblasts derived from sporadic Alzheimer patients and from age-matched control individuals that may mirror changes in the central nervous system. METHODS: Intracellular ionic homeostasis of Alzheimer and control fibroblasts was measured in Fura-2AM-loaded human fibroblasts by dual wavelength spectrofluorimetry. RESULTS: Cells derived from Alzheimer patients exhibited lower intracellular free calcium levels as compared to the control cultures. Exposure of fibroblasts to beta-amyloid resulted in increased calcium concentrations of the control cells, but not of Alzheimer ones. CONCLUSION: Our findings indicate that Alzheimer's disease is a systemic disorder that, among others, affects the calcium homeostasis of fibroblasts. Even though it is unknown whether the diminished ionic response of Alzheimer fibroblasts is a disease or actual status marker, it could prove to be a useful model for the analysis of Alzheimer specific changes.

Palotás A, Kálmán J, Laskay G, Juhász A, Janka Z, Penke B. · Department of Medical Chemistry, University of Szeged, Hungary. · Neurochem Res. · Pubmed #11565613 No free full text.

Abstract: The accumulation of the beta-amyloid peptide (betaAP) in the brain, produced from the ubiquitously expressed amyloid precursor protein (APP) is a defining feature of Alzheimer's disease (AD). Consistent with studies demonstrating the importance of skin biopsy in the diagnosis of neurodegenerative disorders, we investigated whether differences in intracellular free calcium levels ([Ca2+]i) of cultured cutaneous fibroblasts derived from sporadic AD patients and from age-matched control individuals might be present. [Ca2+]i was measured in Fura-2AM-loaded human fibroblasts by dual wavelength spectrofluorimetry. AD cells exhibited lower [Ca2+]i as compared to the control cultures. Exposure of fibroblasts to betaAP resulted in increased [Ca2+]i of the control cells, but not of AD fibroblasts. Our test could prove useful in supporting the diagnosis of (sporadic) AD in patients suspected of suffering from the disease.