Your search for: 'author:("Antúnez, Carmen")' has returned 8 results. (0.009s) Save search

Authors: Antúnez, Carmen | Boada, Mercé | López-Arrieta, Jesús | Ramirez-Lorca, Reposo | Hernández, Isabel | Marín, Juan | Martínez-Lage, Pablo | González-Pérez, Antonio | Jorge Galan, José | Gayán, Javier | Real, Luis M. | Ruiz, Agustín

Article Type: Short Communication

Abstract: GOLPH2 gene SNP variants Rs10868366 and Rs7019241 were reported to decrease the risk of Alzheimer's disease in a recent Whole Genome Association Study. We have investigated these genetic variants in 2470 individuals from Spain to conduct an independent replication study of the proposed SNP markers. We found no evidence of association between GOLPH2 markers and susceptibility to Alzheimer's disease in our series. We concluded that GOLPH2 gene does not contribute to risk of disease in this study sample.

Keywords: Alzheimer's disease, complex diseases, genetic susceptibility, Genome Wide Association Studies (GWAS), GOLPH2, human molecular genetics, neurodegeneration

DOI: 10.3233/JAD-2009-1200

Citation: Journal of Alzheimer's Disease, vol. 18, no. 4, pp. 751-754, 2009

Authors: Boada, Mercè | Antúnez, Carmen | López-Arrieta, Jesús | Galán, José Jorge | Morón, Francisco J. | Hernández, Isabel | Marín, Juan | Martínez-Lage, Pablo | Alegret, Montserrat | Carrasco, Jose M. | Moreno, Concha | Real, Luis M. | González-Pérez, Antonio | Tárraga, Lluís | Ruiz, Agustín

Article Type: Research Article

Abstract: CALHM1 gene coding non-synonymous SNP P86L (rs2986017) was reported to increase the risk of Alzheimer's disease (AD) in a recent study. We have investigated this genetic variant in 2470 individuals from Spain to conduct an independent replication study of the proposed SNP marker. By applying a recessive model, we observed weak evidence of an association between P86L mutation and late-onset AD (LOAD) susceptibility in our case-control study (OR = 1.38 C.I. = [1.01–1.89]). Meta-analysis of available studies also supports a recessive model for CALHM1 P86L variant and provides evidence of between study heterogeneity. Importantly, we found that adjusted mean age …at AD onset in P86L homozygous LOAD patients was significantly earlier that in the rest of patients (77.01 ± 6.1 for P86L homozygous carriers versus 79.0 ± 6.0 for the rest of patients, p = 0.002). We concluded that the CALMH1 gene may contribute to AD risk in our study population. The observed genetic model (recessive) and the estimated magnitude of the effect both imply that virtually all studies performed to date were markedly underpowered to detect this effect and underscore the importance of follow up, replication, and meta-analyses of promising genetic signals. Show more

Keywords: Alzheimer's disease, association, CALHM1, genotype, meta-analysis, molecular genetics, polymorphism

DOI: 10.3233/JAD-2010-1357

Citation: Journal of Alzheimer's Disease, vol. 20, no. 1, pp. 247-251, 2010

Authors: Ramírez-Lorca, Reposo | Boada, Mercé | Antúnez, Carmen | López-Arrieta, Jesús | Moreno-Rey, Concha | Hernández, Isabel | Marín, Juan | Gayán, Javier | González-Pérez, Antonio | Alegret, Montserrat | Tárraga, Lluis | Real, Luis M. | Ruiz, Agustín

Article Type: Short Communication

Abstract: The MTHFD1L gene SNP variant rs11754661 was found to increase the risk of Alzheimer's disease in a recent Whole Genome Association Study [1]. We have carried out an independent study of this genetic variant in 2467 individuals from Spain. We found no evidence of association between the MTHFD1L marker and susceptibility to Alzheimer's disease in our sample.

Keywords: Folate, GWAS, homocysteine, MTHFD1L, population genetics, susceptibility, SNP

DOI: 10.3233/JAD-2011-101983

Citation: Journal of Alzheimer's Disease, vol. 25, no. 1, pp. 47-50, 2011

Authors: Martinez-Mir, Amalia | González-Pérez, Antonio | Gayán, Javier | Antúnez, Carmen | Marín, Juan | Boada, Mercé | Lopez-Arrieta, Jesús María | Alzheimer's Disease Neuroimaging Initiative | Fernández, Evaristo | Ramírez-Lorca, Reposo | Sáez, María Eugenia | Ruiz, Agustín | Scholl, Francisco G. | Real, Luis Miguel

Article Type: Research Article

Abstract: The interaction between neurexins and neuroligins promotes the formation of functional synaptic structures. Recently, it has been reported that neurexins and neuroligins are proteolytically processed by presenilins at synapses. Based on this interaction and the role of presenilins in familial Alzheimer's disease (AD), we hypothesized that dysfunction of the neuroligin-neurexin pathway might be associated with AD. To explore this hypothesis, we carried out a meta-analysis of five genome-wide association studies (GWAS) comprising 1, 256 SNPs in the NRXN1, NRXN2, NRXN3, and NLGN1 genes (3,009 cases and 3,006 control individuals). We identified a marker in the NRXN3 gene (rs17757879) that showed …a consistent protective effect in all GWAS, however, the statistical significance obtained did not resist multiple testing corrections (OR = 0.851, p = 0.002). Nonetheless, gender analysis revealed that this effect was restricted to males. A combined meta-analysis of the former five GWAS together with a replication Spanish sample consisting of 1,785 cases and 1,634 controls confirmed this observation (rs17757879, OR = 0.742, 95% CI = 0.632–0.872, p = 0.00028, final meta-analysis). We conclude that NRXN3 might have a role in susceptibility to AD in males. Show more

Keywords: Alzheimer's disease, genetics, genome-wide association study, meta-analysis, neurexins, neuroligins, NRXN3

DOI: 10.3233/JAD-122257

Citation: Journal of Alzheimer's Disease, vol. 35, no. 2, pp. 403-412, 2013

Authors: Sánchez-Benavides, Gonzalo | Peña-Casanova, Jordi | Casals-Coll, Marta | Gramunt, Nina | Molinuevo, José L. | Gómez-Ansón, Beatriz | Aguilar, Miguel | Robles, Alfredo | Antúnez, Carmen | Martínez-Parra, Carlos | Frank-García, Anna | Fernández-Martínez, Manuel | Blesa, Rafael | for the NEURONORMA Study Team

Article Type: Research Article

Abstract: The aim of this study was to characterize the neuropsychological and neuroimaging profiles of mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients, and to study the magnitude of the differences by comparing both outcomes with healthy subjects in a cross-sectional manner. Five hundred and thirty-five subjects (356 cognitively normal adults (CONT), 79 MCI, and 100 AD) were assessed with the NEURONORMA neuropsychological battery. Thirty CONT, 23 MCI, and 23 AD subjects from this sample were included in the neuroimaging substudy. Patients' raw cognitive scores were converted to age and education-adjusted scaled ones (range 2–18) using co-normed reference values. Medians …were plotted to examine the cognitive profile. MRIs were processed by means of FreeSurfer. Effect size indices (Cohen's d) were calculated in order to compare the standardized differences between patients and healthy subjects. Graphically, the observed cognitive profiles for MCI and AD groups produced near to parallel lines. Verbal and visual memories were the most impaired domains in both groups, followed by executive functions and linguistic/semantic ones. The largest effect size between AD and cognitively normal subjects was found for the FCSRT (d = 4.05, AD versus CONT), which doubled the value obtained by the best MRI measure, the right hippocampus (d = 1.65, AD versus CONT). Our results support the notion of a continuum in cognitive profile between MCI and AD. Neuropsychological outcomes, in particular the FCSRT, are better than neuroimaging ones at detecting differences among subjects. Show more

Keywords: Alzheimer's disease, magnetic resonance imaging, mild cognitive impairment, neuropsychological tests, neuropsychology

DOI: 10.3233/JAD-132186

Citation: Journal of Alzheimer's Disease, vol. 41, no. 3, pp. 887-901, 2014

Authors: Moreno-Grau, Sonia | Barneda, Bruna | Carriba, Paulina | Marín, Juan | Sotolongo-Grau, Oscar | Hernández, Isabel | Rosende-Roca, Maitée | Mauleón, Ana | Vargas, Liliana | Espinosa, Ana | Alegret, Montserrat | Rodriguez, Octavio | Ortega, Gemma | Fernández, Maria Victoria | López-Arrieta, Jesús | Tárraga, Lluís | Boada, Mercè | Antúnez, Carmen | López, Joaquin | Ruiz, Agustín | Comella, Joan Xavier

Article Type: Research Article

Abstract: The objective of this study was to identify genetic variation in genes encoding death receptors and signals that modulate their activity. After conducting a meta-analysis with five previous genome-wide association studies and aggregated data, the most significant signals, (TNF locus: rs2395488, rs2534672, and rs9267445; and FASLG locus: rs730278), were replicated in 1,046 cases and 372 controls. The rs2395488 and rs2534672 markers showed a modest protective effect (OR = 0.849, p = 0.49780; OR = 0.687, p = 0.11335), in contrast to rs730278 marker (OR = 1.146, p = 0.17212), which did not follow the previous effect direction; in any case …it reached the significance level. Final meta-analysis, adding the replication sample, confirmed these observations. We concluded that FASLG marker is not etiologically linked to Alzheimer's disease. However, single nucleotide polymorphisms around TNF locus require further analyses in order to explain the association between Alzheimer's disease and human leukocyte antigen. Show more

Keywords: Alzheimer's disease, apoptosis, death receptors, FASLG, genetics, genome-wide association study, meta-analysis, TNF

DOI: 10.3233/JAD-142721

Citation: Journal of Alzheimer's Disease, vol. 45, no. 2, pp. 621-629, 2015

Authors: Olazarán, Javier | Gil-de-Gómez, Luis | Rodríguez-Martín, Andrés | Valentí-Soler, Meritxell | Frades-Payo, Belén | Marín-Muñoz, Juan | Antúnez, Carmen | Frank-García, Ana | Acedo-Jiménez, Carmen | Morlán-Gracia, Lorenzo | Petidier-Torregrossa, Roberto | Guisasola, María Concepción | Bermejo-Pareja, Félix | Sánchez-Ferro, Álvaro | Pérez-Martínez, David A. | Manzano-Palomo, Sagrario | Farquhar, Ruth | Rábano, Alberto | Calero, Miguel

Article Type: Research Article

Abstract: Accurate blood-based biomarkers of Alzheimer's disease (AD) could constitute simple, inexpensive, and non-invasive tools for the early diagnosis and treatment of this devastating neurodegenerative disease. We sought to develop a robust AD biomarker panel by identifying alterations in plasma metabolites that persist throughout the continuum of AD pathophysiology. Using a multicenter, cross-sectional study design, we based our analysis on metabolites whose levels were altered both in AD patients and in patients with amnestic mild cognitive impairment (aMCI), the earliest identifiable stage of AD. UPLC coupled to mass spectrometry was used to independently compare the levels of 495 plasma metabolites in …aMCI (n = 58) and AD (n = 100) patients with those of normal cognition controls (NC, n = 93). Metabolite alterations common to both aMCI and AD patients were used to generate a logistic regression model that accurately distinguished AD from NC patients. The final panel consisted of seven metabolites: three amino acids (glutamic acid, alanine, and aspartic acid), one non-esterified fatty acid (22:6n-3, DHA), one bile acid (deoxycholic acid), one phosphatidylethanolamine [PE(36:4)], and one sphingomyelin [SM(39:1)]. Detailed analysis ruled out the influence of potential confounding variables, including comorbidities and treatments, on each of the seven biomarkers. The final model accurately distinguished AD from NC patients (AUC, 0.918). Importantly, the model also distinguished aMCI from NC patients (AUC, 0.826), indicating its potential diagnostic utility in early disease stages. These findings describe a sensitive biomarker panel that may facilitate the specific detection of early-stage AD through the analysis of plasma samples. Show more

Keywords: Alzheimer's disease, biomarkers, diagnosis, mild cognitive impairment, plasma

DOI: 10.3233/JAD-142925

Citation: Journal of Alzheimer's Disease, vol. 45, no. 4, pp. 1157-1173, 2015

Authors: Lambert, Jean-Charles | Sleegers, Kristel | González-Pérez, Antonio | Ingelsson, Martin | Beecham, Gary W. | Hiltunen, Mikko | Combarros, Onofre | Bullido, Maria J. | Brouwers, Nathalie | Bettens, Karolien | Berr, Claudine | Pasquier, Florence | Richard, Florence | DeKosky, Steven T. | Hannequin, Didier | Haines, Jonathan L. | Tognoni, Gloria | Fiévet, Nathalie | Dartigues, Jean-François | Tzourio, Christophe | Engelborghs, Sebastiaan | Arosio, Beatrice | Coto, Elicer | De Deyn, Peter | Del Zompo, Maria | Mateo, Ignacio | Boada, Merce | Antunez, Carmen | Lopez-Arrieta, Jesus | Epelbaum, Jacques | Schjeide, Brit-Maren Michaud | Frank-Garcia, Ana | Giedraitis, Vilmentas | Helisalmi, Seppo | Porcellini, Elisa | Pilotto, Alberto | Forti, Paola | Ferri, Raffaele | Delepine, Marc | Zelenika, Diana | Lathrop, Mark | Scarpini, Elio | Siciliano, Gabriele | Solfrizzi, Vincenzo | Sorbi, Sandro | Spalletta, Gianfranco | Ravaglia, Giovanni | Valdivieso, Fernando | Vepsäläinen, Saila | Alvarez, Victoria | Bosco, Paolo | Mancuso, Michelangelo | Panza, Francesco | Nacmias, Benedetta | Bossù, Paola | Hanon, Olivier | Piccardi, Paola | Annoni, Giorgio | Mann, David | Marambaud, Philippe | Seripa, Davide | Galimberti, Daniela | Tanzi, Rudolph E | Bertram, Lars | Lendon, Corinne | Lannfelt, Lars | Licastro, Federico | Campion, Dominique | Pericak-Vance, Margaret A. | Soininen, Hilkka | Van Broeckhoven, Christine | Alpérovitch, Annick | Ruiz, Agustin | Kamboh, M. Ilyas | Amouyel, Philippe

Article Type: Research Article

Abstract: The only established genetic determinant of non-Mendelian forms of Alzheimer's disease (AD) is the ε4 allele of the apolipoprotein E gene (APOE). Recently, it has been reported that the P86L polymorphism of the calcium homeostasis modulator 1 gene (CALHM1) is associated with the risk of developing AD. In order to independently assess this association, we performed a meta-analysis of 7,873 AD cases and 13,274 controls of Caucasian origin (from a total of 24 centers in Belgium, Finland, France, Italy, Spain, Sweden, the UK, and the USA). Our results indicate that the CALHM1 P86L polymorphism is likely not a genetic determinant …of AD but may modulate age of onset by interacting with the effect of the ε4 allele of the APOE gene. Show more

Keywords: Age at onset, Alzheimer's disease, apolipoprotein E, CALHM1, polymorphism

DOI: 10.3233/JAD-2010-100933

Citation: Journal of Alzheimer's Disease, vol. 22, no. 1, pp. 247-255, 2010