Alzheimer Disease: Vassilopoulos D

Paraskevas GP, Kapaki E, Papageorgiou SG, Kalfakis N, Andreadou E, Zalonis I, Vassilopoulos D. · Department of Neurology, School of Medicine, Athens National University, Athens, Greece. · Eur J Neurol. · Pubmed #19146641 No free full text.

Abstract: BACKGROUND AND PURPOSE: The differential diagnosis between vascular dementia (VD) and Alzheimer's disease (AD) or mixed dementia (MD) is not always easy in clinical practice. The purpose of the present study was to evaluate the cerebrospinal fluid (CSF) biomarkers tau protein in its total (tau(T)) or hyperphosphorylated at threonin-181(tau(P-181)) form and beta amyloid peptide 1-42 (A beta 42) alone and their combinations to investigate their diagnostic value in the discrimination between VD and AD or MD. METHODS: The above CSF biomarkers were determined in duplicate and blind to the clinical diagnosis by double sandwich, enzyme-linked immunosorbent assay (ELISA) commercial kits (Innogenetics, Gent, Belgium) in 92 AD patients, 23 VD patients, 17 patients with MD and 68 controls. RESULTS: Alzheimer's disease and MD showed increased levels of tau(T), tau(P) and reduced levels of A beta 42 as compared with the controls. The best discrimination between VD and AD or MD was achieved by the combination of all three biomarkers, correctly classifying >or=85% of patients, either in the form of a discriminant function or in the form of the tau(T) x tau(P-181)/A beta 42 formula. CONCLUSIONS: Cerebrospinal fluid biomarkers may be a useful adjunct for the discrimination between AD/ MD and VD in every day clinical practice.

Poulopoulou C, Davaki P, Sgouropoulos P, Tsaltas E, Nikolaou C, Orfanioutou F, Vassilopoulos D. · Laboratory of Experimental Neurophysiology, Neurology Department, Medical School of Athens, Eginition Hospital, 72-74 Vas. Sophias Avenue, Athens, Greece. · Neurology. · Pubmed #18427074 No free full text.

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Kapaki E, Paraskevas GP, Papageorgiou SG, Bonakis A, Kalfakis N, Zalonis I, Vassilopoulos D. · Department of Neurology, School of Medicine, Athens National University, Eginition Hospital, Athens, Greece. · Alzheimer Dis Assoc Disord. · Pubmed #18317246 No free full text.

Abstract: BACKGROUND: Cerebrospinal fluid (CSF) biomarkers have been increasingly studied in dementia clinical and differential diagnosis. METHODS: We assessed levels of total tau protein (tauT), tau phosphorylated at threonine 181 (tau P-181), and beta-amyloid1-42 (A beta 42) in 34 patients with frontotemporal lobar degeneration (FTLD), 76 Alzheimer disease (AD) cases, and 93 controls (CTRL). Double sandwich enzyme-linked immunosorbent assays (Innogenetics) were used for measurements. RESULTS: Total tau was significantly increased and A beta 42 decreased in FTLD and AD patients as compared with CTRL. CSF tau P-181 levels were significantly increased only in AD. The tauT/A beta 42 ratio successfully discriminated FTLD from CTRL with a 86.7% specificity and 80.6% sensitivity, whereas the tauT alone was more specific (95.7%) but less sensitive (64.75%). For the discrimination of FTLD from AD, tauT/A beta 42 ratio was better (90.3% sensitivity and 64.5% specificity) compared with the other biomarkers alone or in combination, whereas tau P-181 was less sensitive but more specific (68.4% and 85.7%, respectively). Subtype analysis revealed that the most AD-like profile of biomarkers were observed in FTLD with motor neuron signs, whereas the most non-AD profile were observed in patients with primary progressive aphasia. CONCLUSIONS: Combined analysis of CSF biomarkers may be useful for the best possible antemortem discrimination of FTLD from AD.

Simonsen AH, McGuire J, Podust VN, Hagnelius NO, Nilsson TK, Kapaki E, Vassilopoulos D, Waldemar G. · Biomarker Discovery Center Facility, Ciphergen Biosystems Inc., Copenhagen, Denmark. · Dement Geriatr Cogn Disord. · Pubmed #17971664 No free full text.

Abstract: BACKGROUND: An early and accurate diagnosis of Alzheimer's disease (AD) is important in order to initiate symptomatic treatment with currently approved drugs and will be of even greater importance with the advent of disease-modifying compounds. METHODS: Protein profiles of human cerebrospinal fluid samples from patients with AD (n = 85), frontotemporal dementia (n = 20), and healthy controls (n = 32) were analyzed by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to verify previously discovered biomarkers. RESULTS: We verified 15 protein biomarkers that were able to differentiate between AD and controls, and 7 of these 15 markers also differentiated AD from FTD. CONCLUSION: A panel of cerebrospinal fluid protein markers was verified by a proteomics technology which may potentially improve the accuracy of the AD diagnosis.

Economou A, Papageorgiou SG, Karageorgiou C, Vassilopoulos D. · Department of Psychology, School of Philosophy, University of Athens, Athens, Greece. · Cogn Behav Neurol. · Pubmed #17558253 No free full text.

Abstract: OBJECTIVE: To (a) compare patients with amnestic Mild Cognitive Impairment (MCI), mild Alzheimer disease (AD), and a group of healthy elderly persons on nonepisodic memory measures; (b) examine which measures are independent of level of education in the groups studied. BACKGROUND: Episodic memory impairment is a cardinal feature of preclinical AD. However, a number of other cognitive measures are also sensitive to the preclinical stage of AD and deficits in multiple domains characterize AD several years before clinical diagnosis. MATERIALS AND METHODS: Patients with amnestic MCI (N=31), patients with mild probable AD (N=15), and healthy elderly controls (N=27) were compared on nonepisodic memory tasks measuring fluid intelligence, working memory, processing speed, verbal fluency, and visual-perceptual and motor functions. Amnestic MCI patients were selected based on clinical criteria and a subgroup was also selected based on psychometric criteria. RESULTS: Multivariate analyses of covariance, controlling for the effects of age, education, and sex, showed that fluid intelligence, working memory, processing speed, semantic fluency, visual-perceptual function, and complex motor function were significantly worse in the MCI than the elderly control group. Working memory, processing speed, semantic fluency, and complex motor tasks were significantly worse in the mild probable AD than the MCI group. The analyses were corroborated using the psychometrically derived MCI group. CONCLUSIONS: (a) Performance on multiple nonepisodic memory measures is affected in the preclinical stage of AD, indicating that broad cognitive impairment characterizes that stage. (b) Complex motor tasks were independent of level of education in our sample, and may have practical utility in the early detection of dementia.

Kapaki EN, Paraskevas GP, Tzerakis NG, Sfagos C, Seretis A, Kararizou E, Vassilopoulos D. · Department of Neurology, School of Medicine, Athens National University, Athens, Greece. · Eur J Neurol. · Pubmed #17250725 No free full text.

Abstract: The aim of the present study was the quantitation of total tau protein (tau(T)), tau phosphorylated at threonine 181 (tau(P-181)) and beta-amyloid(1-42) (Abeta42) in the cerebrospinal fluid (CSF) of patients with idiopathic normal pressure hydrocephalus (iNPH), Alzheimer's disease (AD) and controls. Double sandwich ELISAs (Innogenetics) were used for the measurements. Total tau was significantly increased in iNPH and highly increased in AD as compared with the control group, whilst Abeta42 was decreased in both diseases. CSF tau(P-181) levels were significantly increased only in AD, but not in iNPH as compared with the controls. A cut-off level for tau(T) at 300 pg/ml, successfully discriminated AD from normal aging with a 95.8% specificity and 91% sensitivity; whilst the tau(P-181)/tau(T) ratio (cut-off value 0.169) was more specific (100%) but less sensitive (92.5%). For the discrimination of iNPH from AD tau(T) achieved low specificity (77.8%) but high sensitivity (92.5%), whilst tau(P-181) (cut-off value 47.4) was both sensitive and specific (88.7% and 86.7% respectively) for the discrimination of these disorders. The present study, despite being clinical, supports the notion that CSF tau(P-181) alone or in combination with tau(T) may be a useful marker in the discrimination of iNPH from AD.

Kapaki E, Paraskevas GP, Mantzou E, Papapostolou A, Alevizaki M, Vassilopoulos D. · Department of Neurology, School of Medicine, Athens National University, "Eginition" Hospital, 74 Vas. Sophias Avenue, Athens 11528, Greece. · Alzheimer Dis Assoc Disord. · Pubmed #17132968 No free full text.

Abstract: Increasing evidence supports an extensive interrelationship between thyroid hormones and the cholinergic system, which is selectively and early affected in Alzheimer disease (AD). The aim of the present study was to explore thyroid function in patients with AD before and after acetylcholinesterase inhibition treatment to possibly identify variances in response. Thyroid function tests were evaluated in 28 AD patients and 24 age and sex-matched controls. Nineteen of the patients were reevaluated after (4 mo) treatment with donepezil. Serum thyrotropin (TSH), triiodothyronine (T3), thyroxine (T4), the free fractions (fT3, fT4) and thyroid autoantibodies were determined using standard methods. All subjects were clinically euthyroid. Patients presented with higher fT4 and anti-thyroperoxidase levels, as compared with the controls. Significant reduction in T4, fT3, fT4, and anti-thyroperoxidase levels were observed 4 months after treatment. Responders had higher T4 and fT4, than nonresponders, followed by significant reductions after treatment. The above, within the normal range alterations, may represent a direct effect on hormone release from the thyroid gland and/or increased conversion of T4 to T3 within the brain. Higher T4 and fT4 levels before treatment might predict a favorable response to donepezil treatment.

Paraskevas GP, Kapaki E, Kararizou E, Mitsonis C, Sfagos C, Vassilopoulos D. · Athens National University, Medical School, Department of Neurology, Eginition Hospital, Greece. · Sex Transm Dis. · Pubmed #16906125 No free full text.

Abstract: OBJECTIVE: The objective of this study was to investigate the levels of tau protein in neurosyphilis. STUDY DESIGN: Total tau protein in the cerebrospinal fluid of 12 patients with neurosyphilis, 17 with syphilis without nervous system involvement, 14 controls, and 14 patients with Alzheimer disease of comparable age were analyzed. Double-sandwich enzyme-linked immunosorbent assay was used for measurements. RESULTS: Increased levels of cerebrospinal fluid total tau were observed in neurosyphilis (median [25th-75th percentile]: 349 pg/mL [312-429]) and in Alzheimer disease (543 [441-1017]) as compared with the controls (189 [106-220]) and syphilis without nervous system involvement (190 [160-223]). Using a cutoff level of 300 pg/mL, increased tau discriminated cases of neurosyphilis from syphilis without nervous system involvement with a sensitivity and specificity of 83% and 94%, respectively. CONCLUSIONS: These results indicate that increased total tau may be useful in the discrimination of neurosyphilis from syphilis without nervous system involvement.

Rentzos M, Zoga M, Paraskevas GP, Kapaki E, Rombos A, Nikolaou C, Tsoutsou A, Vassilopoulos D. · Department of Neurology, Aeginition Hospital-Athens Medical School. · J Geriatr Psychiatry Neurol. · Pubmed #16690997 No free full text.

Abstract: Interleukin-15 is a novel proinflammatory cytokine. It is produced by activated blood monocytes, macrophages, and glial cells. The objective of our study was to assess the role of interleukin-15 as a marker of increased proinflammatory activity in patients with Alzheimer's disease and frontotemporal dementia. We measured cerebrospinal fluid interleukin-15 levels in 17 patients with Alzheimer's disease and 7 patients with frontotemporal dementia in comparison with 17 patients with amyotrophic lateral sclerosis and 15 patients with Parkinson's disease. Patients with Alzheimer's disease and frontotemporal dementia had significantly higher cerebrospinal fluid interleukin-15 levels compared with patients with noninflammatory neurological diseases (P < .05 and P < .01, respectively). In Alzheimer's disease, a significant positive correlation was noted between interleukin-15 levels and age of onset (R = .48, P = .05). Our findings suggest that interleukin-15 may be implicated in the pathophysiology of Alzheimer's disease and frontotemporal dementia.

Rentzos M, Michalopoulou M, Nikolaou C, Cambouri C, Rombos A, Dimitrakopoulos A, Vassilopoulos D. · Department of Neurology, Aeginition Hospital, Athens Medical School, 72-74 Vas.Sophias Av, Greece. · J Neurol Sci. · Pubmed #15694193 No free full text.

Abstract: Immunological disturbances have been implicated in the pathogenesis of some neurodegenerative disorders like Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). Adhesion molecules are markers of activated endothelial cells upregulated by action of cytokines. MATERIALS AND METHODS: To investigate the activation or not of the vascular cells in AD and ALS, serum soluble intercellular adhesion molecule-1 (ICAM-1) and soluble E-selectin were evaluated (enzyme-like immunosorbent assay, ELISA) in 22 patients with Alzheimer's disease (AD), 20 patients with amyotrophic lateral sclerosis (ALS), 34 patients with non-inflammatory neurological diseases (NIND) and 15 control subjects. RESULTS: Patients with AD had higher s-ICAM-1 levels compared to NIND patients and control subjects (p<0.0027 and p<0.04, respectively). Patients with ALS had not higher s-ICAM-1 levels compared to NIND patients and control subjects (p<0.21 and p<0.31, respectively). Soluble-E-selectin levels in AD and ALS patients were not statistically different compared to NIND patients and controls (p<0.4, p<0.9 and p<0.3, p<0.19, respectively). CONCLUSIONS: The presence of high s-ICAM values may be related to immunological processes involved in pathogenetic mechanisms of AD. The not statistically significant values of s-E selectin, a glycoprotein considered an exclusive marker of endothelial activation, seem to suggest the neural rather than the endothelial s-ICAM origin in patients with AD. The low values of s-ICAM-1 and sE-selectin in the serum of ALS patients do not exclude the presence of an unconventional immunological abnormality in this disorder.

Rentzos M, Michalopoulou M, Nikolaou C, Cambouri C, Rombos A, Dimitrakopoulos A, Kapaki E, Vassilopoulos D. · Department of Neurology, Aeginition Hospital, Athens Medical School, Vass. Sophias av. 72-74, 11528 Athens, Greece. · J Geriatr Psychiatry Neurol. · Pubmed #15533994 No free full text.

Abstract: Serum soluble intercellular adhesion molecule-1 (s-ICAM-1) and soluble E-selectin (s-ELAM-1) were evaluated in 25 patients with Alzheimer's disease (AD), 54 patients with noninflammatory neurological diseases (NIND), and 15 control subjects. Patients with AD had a higher s-ICAM-1 level compared with the NIND patients and the control subjects (P< .001 and P< .04, respectively). The presence of high s-ICAM-1 values may be related to immunological processes involved in pathogenetic mechanisms of AD. The not statistically significant values of (s-ELAM-1), a glycoprotein considered an exclusive marker of endothelial activation, compared with the NIND patients and healthy subjects (P< .47 and P< .17, respectively), seem to suggest the neural rather than the endothelial s-ICAM origin in patients with AD.

Petersen MB, Karadima G, Samaritaki M, Avramopoulos D, Vassilopoulos D, Mikkelsen M. · Department of Genetics, Institute of Child Health, Athens, Greece. · Am J Med Genet. · Pubmed #10951459 No free full text.

Abstract: Several lines of evidence suggest a shared genetic susceptibility to Down syndrome (DS) and Alzheimer disease (AD). Rare forms of autosomal-dominant AD are caused by mutations in the APP and presenilin genes (PS-1 and PS-2). The presenilin proteins have been localized to the nuclear membrane, kinetochores, and centrosomes, suggesting a function in chromosome segregation. A genetic association between a polymorphism in intron 8 of the PS-1 gene and AD has been described in some series, and an increased risk of AD has been reported in mothers of DS probands. We therefore studied 168 probands with free trisomy 21 of known parental and meiotic origin and their parents from a population-based material, by analyzing the intron 8 polymorphism in the PS-1 gene. An increased frequency of allele 1 in mothers with a meiosis II error (70.8%) was found compared with mothers with a meiosis I error (52.7%, P < 0.01), with an excess of the 11 genotype in the meiosis II mothers. The frequency of allele 1 in mothers carrying apolipoprotein E (APOE) epsilon4 allele (68.0%) was higher than in mothers without epsilon4 (52.2%, P < 0.01). We hypothesize that the PS-1 intronic polymorphism might be involved in chromosomal nondisjunction through an influence on the expression level of PS-1 or due to linkage disequilibrium with biologically relevant polymorphisms in or outside the PS-1 gene.