Alzheimer Disease: Kapaki E

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.

Verwey NA, van der Flier WM, Blennow K, Clark C, Sokolow S, De Deyn PP, Galasko D, Hampel H, Hartmann T, Kapaki E, Lannfelt L, Mehta PD, Parnetti L, Petzold A, Pirttila T, Saleh L, Skinningsrud A, Swieten JC, Verbeek MM, Wiltfang J, Younkin S, Scheltens P, Blankenstein MA. · Department of Clinical Chemistry, VU University Medical Center, , HV, The Netherlands. · Ann Clin Biochem. · Pubmed #19342441 No free full text.

Abstract: BACKGROUND: Different cerebrospinal fluid (CSF) amyloid-beta 1-42 (Abeta(1-42)), total Tau (Tau) and Tau phosphorylated at threonine 181 (P-Tau) levels are reported, but currently there is a lack of quality control programmes. The aim of this study was to compare the measurements of these CSF biomarkers, between and within centres. METHODS: Three CSF-pool samples were distributed to 13 laboratories in 2004 and the same samples were again distributed to 18 laboratories in 2008. In 2004 six laboratories measured Abeta(1-42), Tau and P-Tau and seven laboratories measured one or two of these marker(s) by enzyme-linked immunosorbent assays (ELISAs). In 2008, 12 laboratories measured all three markers, three laboratories measured one or two marker(s) by ELISAs and three laboratories measured the markers by Luminex. RESULTS: In 2004, the ELISA intercentre coefficients of variance (interCV) were 31%, 21% and 13% for Abeta(1-42), Tau and P-Tau, respectively. These were 37%, 16% and 15%, respectively, in 2008. When we restricted the analysis to the Innotest (N = 13) for Abeta(1-42), lower interCV were calculated (22%). The centres that participated in both years (N = 9) showed interCVs of 21%, 15% and 9% and intra-centre coefficients (intraCV) of variance of 25%,18% and 7% in 2008. CONCLUSIONS: The highest variability was found for Abeta(1-42). The variabilities for Tau and P-Tau were lower in both years. The centres that participated in both years showed a high intraCV comparable to their interCV, indicating that there is not only a high variation between but also within centres. Besides a uniform standardization of (pre)analytical procedures, the same assay should be used to decrease the inter/intracentre variation.

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.

Liappas I, Theotoka I, Kapaki E, Ilias I, Paraskevas GP, Soldatos CR. · Department of Psychiatry, Athens National University, School of Medicine, Eginition Hospital, Athens, Greece. · In Vivo. · Pubmed #18210766 No free full text.

Abstract: BACKGROUND: Heavy and chronic alcohol dependence and Alzheimer's disease may share some neuropsychological characteristics. PATIENTS AND METHODS: The pattern of neuropsychological characteristics of 33 alcohol-dependent patients who reported memory disturbances were evaluated and compared to the neuropsychological performance of 38 patients with mild-stage Alzheimer's disease and 73 healthy subjects, serving as controls. Alcohol-dependent patients were examined with tools concerning the pattern of alcohol abuse and problems related to alcohol consumption. All groups completed a full battery of neuropsychological tests for the assessment of cognitive functions, such as different kinds of memory, attention, executive function etc. RESULTS: Alcohol-dependent patients fared worse compared to the control subjects in every test used. The comparison of alcohol-dependent patients versus patients with Alzheimer's disease showed that the latter are much more burdened, as far as cognition is concerned, in all aspects of memory. CONCLUSION: Alcohol-dependent patients, even if they are not demented, have mild cognitive impairment in all domains of cognition (memory and frontal functions) in comparison with controls which performed within the norms. Verbal fluency, working memory and frontal functions were impaired at the same degree in alcohol-dependent patients and in patients with Alzheimer's disease. Memory problems were more pronounced in Alzheimer's disease patients.

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.

Theotoka I, Kapaki E, Vagenas V, Ilias I, Paraskevas GP, Liappas I. · Department of Psychiatry, Athens University Medical School, Eginition Hospital, Athens, Greece. · Percept Mot Skills. · Pubmed #17688151 No free full text.

Abstract: To validate the Instrumental Activities of Daily Living in Greek, 44 men (M age=70.5 yr., SD=7.2) and 58 women (M age= 68.4, SD=9.2), outpatients of memory clinics, were studied. Sex differences in the item responses were evaluated. Reliability assessed as Cronbach alpha was .84, while validity was assessed by correlation of .77 with the Mini-Mental State Examination. 21 men and 20 women had moderate to severe dementia, with Mini-Mental State Examination scores <20. The results show that this Greek language version can be effectively used in Greece.

Wollmer MA, Sleegers K, Ingelsson M, Zekanowski C, Brouwers N, Maruszak A, Brunner F, Huynh KD, Kilander L, Brundin RM, Hedlund M, Giedraitis V, Glaser A, Engelborghs S, De Deyn PP, Kapaki E, Tsolaki M, Daniilidou M, Molyva D, Paraskevas GP, Thal DR, Barcikowska M, Kuznicki J, Lannfelt L, Van Broeckhoven C, Nitsch RM, Hock C, Papassotiropoulos A. · Division of Psychiatry Research, University of Zürich, August Forel Str. 1, 8008 Zurich, Switzerland. · Neurogenetics. · Pubmed #17387528 No free full text.

Abstract: Alzheimer's disease (AD) is a genetically complex disorder, and several genes related to cholesterol metabolism have been reported to contribute to AD risk. To identify further AD susceptibility genes, we have screened genes that map to chromosomal regions with high logarithm of the odds scores for AD in full genome scans and are related to cholesterol metabolism. In a European screening sample of 115 sporadic AD patients and 191 healthy control subjects, we analyzed single nucleotide polymorphisms in 28 cholesterol-related genes for association with AD. The genes HMGCS2, FDPS, RAFTLIN, ACAD8, NPC2, and ABCG1 were associated with AD at a significance level of P < or = 0.05 in this sample. Replication trials in five independent European samples detected associations of variants within HMGCS2, FDPS, NPC2, or ABCG1 with AD in some samples (P = 0.05 to P = 0.005). We did not identify a marker that was significantly associated with AD in the pooled sample (n = 2864). Stratification of this sample revealed an APOE-dependent association of HMGCS2 with AD (P = 0.004). We conclude that genetic variants investigated in this study may be associated with a moderate modification of the risk for AD in some samples.

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.

Papassotiropoulos A, Lambert JC, Wavrant-De Vrièze F, Wollmer MA, von der Kammer H, Streffer JR, Maddalena A, Huynh KD, Wolleb S, Lutjohann D, Schneider B, Thal DR, Grimaldi LM, Tsolaki M, Kapaki E, Ravid R, Konietzko U, Hegi T, Pasch T, Jung H, Braak H, Amouyel P, Rogaev EI, Hardy J, Hock C, Nitsch RM. · Division of Psychiatry Research, University of Zurich, Zurich, Switzerland. papas@ · Neurodegener Dis. · Pubmed #16909003 No free full text.

Abstract: Alzheimer's disease (AD) is the most common cause of dementia. It is characterized by beta-amyloid (A beta) plaques, neurofibrillary tangles and the degeneration of specifically vulnerable brain neurons. We observed high expression of the cholesterol 25-hydroxylase (CH25H) gene in specifically vulnerable brain regions of AD patients. CH25H maps to a region within 10q23 that has been previously linked to sporadic AD. Sequencing of the 5' region of CH25H revealed three common haplotypes, CH25Hchi2, CH25Hchi3 and CH25Hchi4; CSF levels of the cholesterol precursor lathosterol were higher in carriers of the CH25Hchi4 haplotype. In 1,282 patients with AD and 1,312 healthy control subjects from five independent populations, a common variation in the vicinity of CH25H was significantly associated with the risk for sporadic AD (p = 0.006). Quantitative neuropathology of brains from elderly non-demented subjects showed brain A beta deposits in carriers of CH25Hchi4 and CH25Hchi3 haplotypes, whereas no A beta deposits were present in CH25Hchi2 carriers. Together, these results are compatible with a role of CH25Hchi4 as a putative susceptibility factor for sporadic AD; they may explain part of the linkage of chromosome 10 markers with sporadic AD, and they suggest the possibility that CH25H polymorphisms are associated with different rates of brain A beta deposition.

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, Paraskevas GP, Kapaki E, Nikolaou C, Zoga M, Rombos A, Tsoutsou A, Vassilopoulos D D. · Department of Neurology, Aeginition Hospital, Athens National University, School of Medicine, 72-74 Vas. Sophias Ave, Athens 11528, Greece. · J Neurol Sci. · Pubmed #16843497 No free full text.

Abstract: Interleukin-12 is a heterodimeric cytokine produced by activated blood monocytes, macrophages and glial cells. It enhances differentiation and proliferation of T cells and increases production of proinflammatory cytokines, such as Interferon-gamma and Tumor Necrosis Factor-alpha. There is little information about the involvement of IL-12 in the pathophysiology of Alzheimer's disease (AD) and other tauopathies. OBJECTIVES: The objective of our study was to assess the role of IL-12 as a potential marker of immune reactions in patients with AD and frontotemporal dementia (FTD). PATIENTS AND METHODS: We measured by immunoassay cerebrospinal fluid (CSF) IL-12 levels in 19 patients with AD and 7 patients with FTD in comparison with CSF IL-12 levels in 30 patients with non-inflammatory neurological diseases served as neurological control patients (NCTRL). IL-12 levels were correlated with age, age of disease onset, disease duration, MMSE score, and rate of dementia progression. Abeta42 and Total tau (tau(T)) levels in CSF were also measured. RESULTS: Patients with AD had significantly lower CSF IL-12 levels compared with NCTRL patients (p<0.001). Patients with FTD had also lower CSF IL-12 levels compared with NCTRL patients (p<0.05). Age, sex, disease duration and MMSE score did not affect IL-12 levels in any of the groups. In AD a significant positive correlation was noted between IL-12 levels and tau(T) levels (Rs=0.46, p=0.048). CONCLUSIONS: Our findings may suggest a reduced inflammatory reaction during the course of AD and FTD. A neurotrophic role of IL-12 and other proinflammatory cytokines cannot be excluded.

Wollmer MA, Kapaki E, Hersberger M, Muntwyler J, Brunner F, Tsolaki M, Akatsu H, Kosaka K, Michikawa M, Molyva D, Paraskevas GP, Lütjohann D, von Eckardstein A, Hock C, Nitsch RM, Papassotiropoulos A. · Division of Psychiatry Research, University of Zürich, Switzerland. · Am J Med Genet B Neuropsychiatr Genet. · Pubmed #16752360 No free full text.

Abstract: A recent study demonstrated a significant genetic association between the ATP-binding cassette transporter A2 (ABCA2) and the risk for Alzheimer's disease (AD) in a large Caucasian sample. The rare T allele of the synonymous exonic single nucleotide polymorphism (SNP) rs908832 was overrepresented in early-onset AD patients as compared to cognitively healthy controls. Here we confirm the association of rs908832 with AD in a Western European population (n = 291, P = 0.008). In a second sample from Southern Europe, rs908832 was not associated with AD. Interestingly, rs908832 was not polymorphic in a Japanese sample. Furthermore, rs908832 was not associated with either serum cholesterol levels or with the risk for coronary artery disease, but seemed to be related to cholesterol levels in the cerebrospinal fluid. These data suggest that ABCA2 may exert population-dependent effects on the genetic risk for sporadic AD and support a role of ABC lipid transporters in the pathogenesis of this disease.

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.

Kapaki E, Liappas I, Paraskevas GP, Theotoka I, Rabavilas A. · Department of Neurology, Athens National University, School of Medicine, Eginition Hospital, Athens, Greece. · Int J Geriatr Psychiatry. · Pubmed #16035118 No free full text.

Abstract: BACKGROUND: Chronic and heavy alcohol abuse or dependence may result in impaired cognition and dementia. The increased risk of Alzheimer's disease (AD) in older individuals interferes with the differential diagnosis, especially when dealing with elderly patients with a long history of alcohol abuse. The aim of the present study was to evaluate the diagnostic value of the putative cerebrospinal fluid (CSF) biomarkers tau, beta-amyloid 1-42 (Abeta42) and their ratio in differentiating alcohol related cognitive disorder (ARCD) from AD. METHODS: Double-sandwich ELISA (Innotest htau antigen and beta-Amyloid (1-42), Innogenetics) were used to quantify the above markers in a total of 20 patients with ARCD, 33 AD patients with mild to moderate dementia and 50 mentally intact subjects. RESULTS: Tau protein successfully differentiated AD from normal ageing with 96% specificity and 93.9% sensitivity and from ARCD with 95% specificity, and 87.9% sensitivity. Abeta42 alone had a specificity of 88% and a sensitivity of 69.7% in differentiating AD from normal ageing, while the corresponding values for differentiating AD from ARCD were 80% and 84.8% respectively. The tau/Abeta42 ratio was better than tau alone for differentiating AD from normal ageing (specificity 94%, sensitivity 97%) and better than any of the candidate markers alone, for differentiating AD from ARCD (specificity 100%, sensitivity 97%). CONCLUSIONS: The combined use of CSF tau and Abeta42 may be a useful tool in the differential diagnosis of ARCD from AD, especially in the early stages, where diagnostic uncertainty is greater.

Kapaki E, Paraskevas GP. · Athens National University, School of Medicine, Department of Neurology, Eginition Hospital, 74 Vas. Sophias Ave., Athens 11528, Greece. · Curr Med Res Opin. · Pubmed #15969887 No free full text.

Abstract: OBJECTIVE: Cholinesterase inhibitors (ChEIs) are the treatment of choice in Alzheimer's disease (AD). Their efficacy has been proven in many clinical trials. The aim of the present study was to confirm their cognitive benefit in every day practice as to whether it is similar to that expected from clinical trials. PATIENTS AND METHODS: We reviewed the files of 41 patients suffering from AD or mixed dementia and treated by ChEIs in terms of every day practice. RESULTS: During the first year MMSE scores remained better than or at baseline levels. Following that a gradual decline was noted. However, at any time point, the observed scores were significantly better than the expected ones calculated according to the pre-treatment rate of decline. The post-treatment rate of decline was significantly better than the pre-treatment one, while progression to the next stage of dementia was delayed by 8 months. CONCLUSION: The present observations from every-day practice indicate that there is a small but significant effect of ChEIs in cognition, similar to that observed in clinical trials. Furthermore, a small but significant delay in dementia progression may occur after treatment with ChEIs.

Finckh U, Kuschel C, Anagnostouli M, Patsouris E, Pantes GV, Gatzonis S, Kapaki E, Davaki P, Lamszus K, Stavrou D, Gal A. · Institute of Human Genetics, University Hospital Hamburg-Eppendorf, University of Hamburg, Butenfeld 42, 22529 Hamburg, Germany. · Neurogenetics. · Pubmed #15776278 No free full text.

Abstract: Twenty-one unrelated patients with a history of suspected familial Alzheimer disease (FAD) were screened for mutations in PSEN1, PSEN2, and APP, the known FAD genes encoding the presenilins (PS1 and PS2) and the amyloid precursor protein (APP). The mutation detection rate was 57%. Of the nine pathogenic mutations found in 12 cases, three were in APP, one in PSEN2, and five in PSEN1, including two novel Greek mutations (L113Q and N135S). Whereas our findings suggest the possibility of single founders for the majority of mutations, we found evidence of recurrence of the APP mutations V717L and V717I.

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.

Kapaki E, Ilias I, Paraskevas GP, Theotoka I, Christakopoulou I. · Athens National University, Medical School, Department of Neurology, Eginition Hospital, Athens GR-11528, Greece. · Acta Neurobiol Exp (Wars). · Pubmed #15053263 links to  free full text

Abstract: The aim of the present study was to explore a possible interplay between cholinesterase inhibitors (ChEIs) and thyroid function tests (TFTs) in patients with Alzheimer's disease (AD). We reviewed thyroid function tests in 19 patients with AD before and after treatment (Rx) with ChEIs. Immunoradiometric assays were used for measuring serum thyrotropin, free thyroxin (FT4) and free triiodothyronine (FT3). Significant differences were observed among FT3 levels according to the duration of therapy. Subtle variations in thyroid function tests--before and after therapy--could be possibly related to ChEIs-induced altered thyroid function.

Kapaki E, Paraskevas GP, Zalonis I, Zournas C. · Department of Neurology, Athens National University, Aeginition Hospital, Athens, Greece. · Eur J Neurol. · Pubmed #12603286 No free full text.

Abstract: Cerebrospinal fluid (CSF) levels of tau protein and amyloid beta(1-42) peptide (Abeta42) have been suggested as possible diagnostic markers of Alzheimer's disease (AD). In order to evaluate their diagnostic potential in clinical practice, we measured tau and Abeta42 levels in the CSF of 49 AD patients, 15 patients with non-AD neurodegenerative dementias (NAND), six patients with vascular dementia (VD) and 49 elderly controls. All the subjects were of Greek origin. A marked increase in tau, a decrease in Abeta42 and a marked increase in the tau/Abeta42 ratio was noted in AD. Abeta42 alone had a specificity of 80% and a sensitivity of 82% in differentiating AD from normal ageing, whilst the corresponding values for differentiating AD from NAND or VD were 80 and 71, or 67 and 82%, respectively. Tau was better in differentiating AD, from normal ageing (specificity 96%, sensitivity 88%), NAND (specificity 93%, sensitivity 71%) and VD (specificity 83%, sensitivity 94%). The tau/Abeta42 ratio achieved values comparable or even better than tau for differentiating AD from normal ageing (specificity 86%, sensitivity 96%) and VD (specificity 83%, sensitivity 90%) and definitely better than any of the candidate markers alone, for differentiating AD from NAND (specificity 100%, sensitivity 71%). Thus, the combined use of CSF tau and Abeta42 in the form of the tau/Abeta42 ratio is a simple, safe and useful adjuvant to clinical criteria for dementia diagnosis.

Wollmer MA, Papassotiropoulos A, Streffer JR, Grimaldi LM, Kapaki E, Salani G, Paraskevas GP, Maddalena A, de Quervain D, Bieber C, Umbricht D, Lemke U, Bosshardt S, Degonda N, Henke K, Hegi T, Jung HH, Pasch T, Hock C, Nitsch RM. · Division of Psychiatry Research, University of Zurich, Switzerland. · Psychiatr Genet. · Pubmed #12218659 No free full text.

Abstract: Tissue inhibitor of metalloproteinases 1 (TIMP-1) inhibits several proteinases including a disintegrin and metalloproteinase 10 (ADAM10), a major alpha-secretase that cleaves the beta-amyloid precursor protein within its amyloidogenic Abeta domain. The gene encoding TIMP-1 (TIMP 1) maps to the short arm of the X chromosome, in a region previously suggested as conferring genetic susceptibility for Alzheimer's disease (AD). To determine whether genetic variability of TIMP 1 contributes to the pathogenesis of AD, we analysed one single nucleotide polymorphism within TIMP 1 and one single nucleotide polymorphism in the 5'-untranslated region of TIMP 1 in patients with AD and control subjects from two independent and ethnically different populations. We did not observe any association between TIMP 1 genotypes and the diagnosis of AD in men or women. We also measured TIMP-1 protein levels in the cerebrospinal fluid of patients with AD, healthy control subjects, and patients with other neurological disorders. TIMP-1 levels were similar in all groups. In addition, no significant differences were observed after stratification for TIMP 1 genotypes. Our data show that neither genetic variability nor protein levels of TIMP-1 are associated with AD.

Kapaki E, Kilidireas K, Paraskevas GP, Michalopoulou M, Patsouris E. · Department of Neurology, Athens National University, Medical School, Aeginition Hospital, 74 Vas Sophias Avenue, 11528 Athens, Greece. · J Neurol Neurosurg Psychiatry. · Pubmed #11511720 links to  free full text

Abstract: The aim was to quantify tau protein and beta-amyloid (Abeta42) in the CSF of patients with sporadic Creutzfeldt-Jakob disease (CJD), Alzheimer's disease (AD), and controls. Double sandwich enzyme linked immunosorbent assays (ELISAs) were used for measurements. Tau was increased 58-fold in CJD and 3.5-fold in AD compared with controls, whereas Abeta42 was decreased 0.5-fold in both CJD and AD. A cut off level for tau protein at 2131 pg/ml successfully discriminated CJD from AD (100% specificity and 93% sensitivity). Tau protein concentration in CSF is probably an additional useful marker in differentiating CJD from AD.