Search

Your search keyword '"Porcellini E"' showing total 163 results
Start Over Author "Porcellini E"
163 results on '"Porcellini E"'

1. Neopterin Levels and Immune Activation in the Blood of Children with Down’s Syndrome

Author

Licastro F., Chiappelli M., Porcellini E., Rustica M., and Corsi M.M.

Subjects
down's syndrome. alzheimer's disease, il-6, crp, neopterin, plasma levels, Crystallography, QD901-999
Abstract

Patients with AD often show altered levels of some immune molecules in their peripheral blood which correlate with cognitive impairment. Downs' syndrome (DS) subjects are at high risk of developing Alzheimer's disease (AD). Here we studied immune molecules, such as interleukin-6 (IL-6), C reactive protein (CRP) and neopterin, in the blood of non demented children with DS to investigate whether altered peripheral immune phenotype could be present in this subjects without dementia, many years before the presentation of clinical signs of cognitive deterioration. Plasma levels of neopterin and IL-6 were measured by commercially available ELISA kits, whereas plasma CRP concentration was evaluated by nephelometric immunoassay technique. We studied a group of 40 patients with DS, 20 healthy controls and 100 patients w ith AD. Plasma levels of IL-6 and CRP were significantly higher in DS than in control children. The increase of IL-6 and CRP from DS children was similar to that found in elderly patients with clinical AD. In the present research we have also studied blood levels of neopterin which were in the normal range either in DS or control. Increased or normal levels of this metabolite have been found in the blood of AD patients. However, increased blood neopterin was likely to be only elevated in patients with advanced clinical stage of AD. Peripheral altered immune phenotype in healthy young subjects with DS might be an early sign of CNS alterations leading many years later to cognitive deterioration and dementia.

Published
2005
Full Text
View/download PDF

4. APOE and Alzheimer disease: a major gene with semi-dominant inheritance

Author

Genin, E, Hannequin, D, Wallon, D, Sleegers, K, Hiltunen, M, Combarros, O, Bullido, M J, Engelborghs, S, De Deyn, P, Berr, C, Pasquier, F, Dubois, B, Tognoni, G, Fiévet, N, Brouwers, N, Bettens, K, Arosio, B, Coto, E, Del Zompo, M, Mateo, I, Epelbaum, J, Frank-Garcia, A, Helisalmi, S, Porcellini, E, Pilotto, A, Forti, P, Ferri, R, Scarpini, E, Siciliano, G, Solfrizzi, V, Sorbi, S, Spalletta, G, Valdivieso, F, Vepsäläinen, S, Alvarez, V, Bosco, P, Mancuso, M, Panza, F, Nacmias, B, Bossù, P, Hanon, O, Piccardi, P, Annoni, G, Seripa, D, Galimberti, D, Licastro, F, Soininen, H, Dartigues, J-F, Kamboh, M I, Van Broeckhoven, C, Lambert, J C, Amouyel, P, and Campion, D

Published
2011
Full Text
View/download PDF

5. The structure of the Shiga toxin 2a A‐subunit dictates the interactions of the toxin with blood components

Author

Brigotti M., Orth-Holler D., Carnicelli D., Porcellini E., Galassi E., Tazzari P. L., Ricci F., Manoli F., Manet I., Talasz H., Lindner H. H., Speth C., Erbeznik T., Fuchs S., Posch W., Chatterjee S., Wurzner R., Brigotti M., Orth-Holler D., Carnicelli D., Porcellini E., Galassi E., Tazzari P.L., Ricci F., Manoli F., Manet I., Talasz H., Lindner H.H., Speth C., Erbeznik T., Fuchs S., Posch W., Chatterjee S., and Wurzner R.

Subjects
Blood Platelets, protein fluorescence, Neutrophils, Protein Conformation, Circular Dichroism, Trihexosylceramides, shiga toxin, Hemolytic uremic syndrome, Shiga toxin-producing Escherichia coli, bacterial toxins, complement factor H, neutrophils, Shiga Toxin 2, Fluorescence, Complement Factor H, Chlorocebus aethiops, Escherichia coli, Leukocytes, Animals, Humans, Trypsin, Vero Cells, Research Articles, Research Article, Protein Binding
Abstract

Hemolytic uremic syndrome (eHUS) is a severe complication of human infections with Shiga toxins (Stxs)‐producing Escherichia coli. A key step in the pathogenesis of eHUS is the interaction of Stxs with blood components before the targeting of renal endothelial cells. Here, we show that a single proteolytic cleavage in the Stx2a A‐subunit, resulting into two fragments (A1 and A2) linked by a disulfide bridge (cleaved Stx2a), dictates different binding abilities. Uncleaved Stx2a was confirmed to bind to human neutrophils and to trigger leukocyte/platelet aggregate formation, whereas cleaved Stx2a was ineffective. Conversely, binding of complement factor H was confirmed for cleaved Stx2a and not for uncleaved Stx2a. It is worth noting that uncleaved and cleaved Stx2a showed no differences in cytotoxicity for Vero cells or Raji cells, structural conformation, and contaminating endotoxin. These results have been obtained by comparing two Stx2a batches, purified in different laboratories by using different protocols, termed Stx2a(cl; cleaved toxin, Innsbruck) and Stx2a(uncl; uncleaved toxin, Bologna). Stx2a(uncl) behaved as Stx2a(cl) after mild trypsin treatment. In this light, previous controversial results obtained with purified Stx2a has to be critically re‐evaluated; furthermore, characterisation of the structure of circulating Stx2a is mandatory to understand eHUS‐pathogenesis and to develop therapeutic approaches.

Published
2019

7. KRAS and ERBB-family genetic alterations affect response to PD-1 inhibitors in metastatic non-squamous NSCLC

Author

Cinausero, M., primary, Laprovitera, N., additional, De Maglio, G., additional, Gerratana, L., additional, Riefolo, M., additional, Macerelli, M., additional, Fiorentino, M., additional, Porcellini, E., additional, Buoro, V., additional, Gelsomino, F., additional, Squadrilli, A., additional, Fasola, G., additional, Tiseo, M., additional, Ferracin, M., additional, and Ardizzoni, A., additional

Published
2019
Full Text
View/download PDF

8. Genome-wide association study indentifies variants at CLU and CR1 associated with Alzheimer’s disease

Author

Lambert JC, Heath S, Even G, Campion D, Sleegers K, Hiltunen M, Combarros O, Zelenika D, Bullido MJ, Tavernier B, Letenneur L, Bettens K, Berr C, Pasquier F, Fiévet N, Barberger-Gateau P, Engelborghs S, De Deyn P, Mateo I, Franck A, Helisalmi S, Porcellini E, Hanon O, European Alzheimer's Disease Initiative Investigators, de Pancorbo MM, Lendon C, Dufouil C, Jaillard C, Leveillard T, Alvarez V, Bosco P, Mancuso M, Panza F, Nacmias B, Bossù P, Piccardi P, Annoni G, Seripa D, Galimberti D, Hannequin D, Licastro F, Soininen H, Ritchie K, Blanché H, Dartigues JF, Tzourio C, Gut I, Van Broeckhoven C, Alpérovitch A, Lathrop M, Amouyel P, FORTI, PAOLA, Lambert, J, Heath, S, Even, G, Campion, D, Sleegers, K, Hiltunen, M, Cambarros, O, Zelenika, D, Bullido, M, Tavernier, B, Letenneur, L, Bettens, K, Berr, C, Pasquier, F, Fiévet, N, Barbager Gateau, P, Engelborghs, S, De Deyn, P, Mateo, I, Franck, A, Helisalmi, S, Porcellini, E, Hanon, O, the European Alzheimer’s disease Initiative, I, de Pancorbo, M, Lendon, C, Dufouil, C, Jaillard, C, Leveillard, T, Alvarez, V, Bosco, P, Mancuso, M, Panza, F, Nacmias, B, Bossù, P, Piccardi, P, Annoni, G, Seripa, D, Galimberti, D, Hannequin, D, Licastro, F, Soininen, H, Ritchie, K, Blanché, H, Dartigues, J, Tzourio, C, Gut, I, Broeckhoven, C, Alpérovitch, A, Lathrop, M, Amouyel, P, Lambert JC, Heath S, Even G, Campion D, Sleegers K, Hiltunen M, Combarros O, Zelenika D, Bullido MJ, Tavernier B, Letenneur L, Bettens K, Berr C, Pasquier F, Fiévet N, Barberger-Gateau P, Engelborghs S, De Deyn P, Mateo I, Franck A, Helisalmi S, Porcellini E, Hanon O, European Alzheimer's Disease Initiative Investigator, de Pancorbo MM, Lendon C, Dufouil C, Jaillard C, Leveillard T, Alvarez V, Bosco P, Mancuso M, Panza F, Nacmias B, Bossù P, Piccardi P, Annoni G, Seripa D, Galimberti D, Hannequin D, Licastro F, Soininen H, Ritchie K, Blanché H, Dartigues JF, Tzourio C, Gut I, Van Broeckhoven C, Alpérovitch A, Lathrop M, Amouyel P, Electronics and Informatics, Clinical sciences, Neurology, and Pathologic Biochemistry and Physiology

Subjects
Apolipoprotein E, SORL1, Genome-wide association study, Disease, Polymorphism, Single Nucleotide, White People, ABCA7, PICALM, Alzheimer Disease, Genetics, Humans, Genetic Predisposition to Disease, European Continental Ancestry Group/genetics, Alzheimer's disease, genome-wide association, APOE, APOJ, Medicine(all), Alzheimer Disease/genetics, biology, Phosphatidylinositol binding, Clusterin, Haplotypes, Receptors, Complement 3b, biology.protein, Human medicine, Clusterin/genetics, Receptors, Complement 3b/genetics, Genome-Wide Association Study
Abstract

The gene encoding apolipoprotein E (APOE) on chromosome 19 is the only confirmed susceptibility locus for late-onset Alzheimer's disease. To identify other risk loci, we conducted a large genome-wide association study of 2,032 individuals from France with Alzheimer's disease (cases) and 5,328 controls. Markers outside APOE with suggestive evidence of association (P 10 5) were examined in collections from Belgium, Finland, Italy and Spain totaling 3,978 Alzheimer's disease cases and 3,297 controls. Two loci gave replicated evidence of association: one within CLU (also called APOJ), encoding clusterin or apolipoprotein J, on chromosome 8 (rs11136000, OR = 0.86, 95% CI 0.81-0.90, P = 7.5 × 10 9 for combined data) and the other within CR1, encoding the complement component (3b/4b) receptor 1, on chromosome 1 (rs6656401, OR = 1.21, 95% CI 1.14-1.29, P = 3.7 × 10 9 for combined data). Previous biological studies support roles of CLU and CR1 in the clearance of Β amyloid (AΒ) peptide, the principal constituent of amyloid plaques, which are one of the major brain lesions of individuals with Alzheimer's disease. © 2009 Nature America, Inc. All rights reserved.

Published
2009

12. The CALHM1 P86L polymorphism is a genetic modifier of age at onset in Alzheimer's disease: a meta-analysis study

Author

Lambert, J., Sleegers, K., Gonzalez-Perez, A., Ingelsson, M., Beecham, G., Hiltunen, M., Combarros, O., Bullido, M., Brouwers, N., Bettens, K., Berr, C., Pasquier, F., Richard, F., Dekosky, S., Hannequin, D., Haines, J., Tognoni, G., Fievet, N., Dartigues, J., Tzourio, C., Engelborghs, S., Arosio, B., Coto, E., De Deyn, P., Del Zompo, M., Mateo, I., Boada, M., Antunez, C., Lopez-Arrieta, J., Epelbaum, J., Schjeide, B., Frank-Garcia, A., Giedraitis, V., Helisalmi, S., Porcellini, E., Pilotto, A., Forti, P., Ferri, R., Delepine, M., Zelenika, D., Lathrop, M., Scarpini, E., Siciliano, G., Solfrizzi, V., Sorbi, S., Spalletta, G., Ravaglia, G., Valdivieso, F., Vepsalainen, S., Alvarez, V., Bosco, P., Mancuso, M., Panza, F., Nacmias, B., Bossu, P., Hanon, O., Piccardi, P., Annoni, G., Mann, D., Marambaud, P., Seripa, D., Galimberti, D., Tanzi, R., Bertram, L., Lendon, C., Lannfelt, L., Licastro, F., Campion, D., Pericak-Vance, M., Soininen, H., Van Broeckhoven, C., Alperovitch, A., Ruiz, A., Kamboh, M., and Amouyel, P.

Subjects
lipids (amino acids, peptides, and proteins)
Abstract

The only established genetic determinant of non-Mendelian forms of Alzheimer's disease (AD) is the epsilon4 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 epsilon4 allele of the APOE gene.

Published
2010

13. Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease

Author

Lambert, Jc, Heath, S, Even, G, Campion, D, Sleegers, K, Hiltunen, M, Combarros, O, Zelenika, D, Bullido, Mj, Tavernier, B, Letenneur, L, Bettens, K, Berr, C, Pasquier, F, Fiévet, N, BARBERGER GATEAU, P, Engelborghs, S, DE DEYN, P, Mateo, I, Franck, A, Helisalmi, S, Porcellini, E, Hanon, O, Siciliano, Gabriele, DE PANCORBO MM, Lendon, C, Dufouil, C, Jaillard, C, Leveillard, T, Alvarez, V, Bosco, P, Mancuso, Michelangelo, Panza, F, Nacmias, B, Bossù, P, Piccardi, P, Annoni, G, Seripa, D, Galimberti, D, Hannequin, D, Licastro, F, Soininen, H, Ritchie, K, Blanché, H, Dartigues, Jf, Tzourio, C, Gut, I, VAN BROECKHOVEN, C, Alpérovitch, A, Lathrop, M, and Amouyel, P.

Published
2009

22. Evidence of the association of BIN1 and PICALM with the AD risk in contrasting European populations

Author

Lambert, J, Zelenika, D, Hiltunen, M, Chouraki, V, Combarros, O, Bullido, M, Tognoni, G, Fiévet, N, Boland, A, Arosio, B, Coto, E, Zompo, M, Mateo, I, Frank Garcia, A, Helisalmi, S, Porcellini, E, Pilotto, A, Forti, P, Ferri, R, Delepine, M, Scarpini, E, Siciliano, G, Solfrizzi, V, Sorbi, S, Spalletta, G, Ravaglia, G, Valdivieso, F, Alvarez, V, Bosco, P, Mancuso, M, Panza, F, Nacmias, B, Bossù, P, Piccardi, P, Annoni, G, Seripa, D, Galimberti, D, Licastro, F, Lathrop, M, Soininen, H, Amouyel, P, Bullido, MJ, Zompo, MD, ANNONI, GIORGIO, Amouyel, P., Lambert, J, Zelenika, D, Hiltunen, M, Chouraki, V, Combarros, O, Bullido, M, Tognoni, G, Fiévet, N, Boland, A, Arosio, B, Coto, E, Zompo, M, Mateo, I, Frank Garcia, A, Helisalmi, S, Porcellini, E, Pilotto, A, Forti, P, Ferri, R, Delepine, M, Scarpini, E, Siciliano, G, Solfrizzi, V, Sorbi, S, Spalletta, G, Ravaglia, G, Valdivieso, F, Alvarez, V, Bosco, P, Mancuso, M, Panza, F, Nacmias, B, Bossù, P, Piccardi, P, Annoni, G, Seripa, D, Galimberti, D, Licastro, F, Lathrop, M, Soininen, H, Amouyel, P, Bullido, MJ, Zompo, MD, ANNONI, GIORGIO, and Amouyel, P.

Abstract

Recent genome-wide association studies have identified 5 loci (BIN1, CLU, CR1, EXOC3L2, and PICALM) as genetic determinants of Alzheimer's disease (AD). We attempted to confirm the association between these genes and the AD risk in 3 contrasting European populations (from Finland, Italy, and Spain). Because CLU and CR1 had already been analyzed in these populations, we restricted our investigation to BIN1, EXO2CL3, and PICALM. In a total of 2816 AD cases and 2706 controls, we unambiguously replicated the association of rs744373 (for BIN1) and rs541458 (for PICALM) polymorphisms with the AD risk (odds ratio [OR] = 1.26, 95% confidence interval [CI] [1.15-1.38], p = 2.9 × 10-7, and OR = 0.80, 95% CI [0.74-0.88], p = 4.6 × 10-7, respectively). In a meta-analysis, rs597668 (EXOC3L2) was also associated with the AD risk, albeit to a lesser extent (OR = 1.19, 95% CI [1.06-1.32], p = 2.0 × 10-3). However, this signal did not appear to be independent of APOE. In conclusion, we confirmed that BIN1 and PICALM are genetic determinants of AD, whereas the potential involvement of EXOC3L2 requires further investigation. © 2011 Elsevier Inc.

Published
2011

23. Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease

Author

Hollingworth, P, Harold, D, Sims, R, Gerrish, A, Lambert, J, Carrasquillo, M, Abraham, R, Hamshere, M, Pahwa, J, Moskvina, V, Dowzell, K, Jones, N, Stretton, A, Thomas, C, Richards, A, Ivanov, D, Widdowson, C, Chapman, J, Lovestone, S, Powell, J, Proitsi, P, Lupton, M, Brayne, C, Rubinsztein, D, Gill, M, Lawlor, B, Lynch, A, Brown, K, Passmore, P, Craig, D, Mcguinness, B, Todd, S, Holmes, C, Mann, D, Smith, A, Beaumont, H, Warden, D, Wilcock, G, Love, S, Kehoe, P, Hooper, N, Vardy, E, Hardy, J, Mead, S, Fox, N, Rossor, M, Collinge, J, Maier, W, Jessen, F, Rüther, E, Schürmann, B, Heun, R, Kölsch, H, van den Bussche, H, Heuser, I, Kornhuber, J, Wiltfang, J, Dichgans, M, Frölich, L, Hampel, H, Gallacher, J, Hüll, M, Rujescu, D, Giegling, I, Goate, A, Kauwe, J, Cruchaga, C, Nowotny, P, Morris, J, Mayo, K, Sleegers, K, Bettens, K, Engelborghs, S, De Deyn, P, Van Broeckhoven, C, Livingston, G, Bass, N, Gurling, H, Mcquillin, A, Gwilliam, R, Deloukas, P, Al Chalabi, A, Shaw, C, Tsolaki, M, Singleton, A, Guerreiro, R, Mühleisen, T, Nöthen, M, Moebus, S, Jöckel, K, Klopp, N, Wichmann, H, Pankratz, V, Sando, S, Aasly, J, Barcikowska, M, Wszolek, Z, Dickson, D, Graff Radford, N, Petersen, R, van Duijn, C, Breteler, M, Ikram, M, Destefano, A, Fitzpatrick, A, Lopez, O, Launer, L, Seshadri, S, Berr, C, Campion, D, Epelbaum, J, Dartigues, J, Tzourio, C, Alpérovitch, A, Lathrop, M, Feulner, T, Friedrich, P, Riehle, C, Krawczak, M, Schreiber, S, Mayhaus, M, Nicolhaus, S, Wagenpfeil, S, Steinberg, S, Stefansson, H, Stefansson, K, Snædal, J, Björnsson, S, Jonsson, P, Chouraki, V, Genier Boley, B, Hiltunen, M, Soininen, H, Combarros, O, Zelenika, D, Delepine, M, Bullido, M, Pasquier, F, Mateo, I, Frank Garcia, A, Porcellini, E, Hanon, O, Coto, E, Alvarez, V, Bosco, P, Siciliano, G, Mancuso, M, Panza, F, Solfrizzi, V, Nacmias, B, Sorbi, S, Bossù, P, Piccardi, P, Arosio, B, Annoni, G, Seripa, D, Pilotto, A, Scarpini, E, Galimberti, D, Brice, A, Hannequin, D, Licastro, F, Jones, L, Holmans, P, Jonsson, T, Riemenschneider, M, Morgan, K, Younkin, S, Owen, M, O'Donovan, M, Amouyel, P, Williams, J, Carrasquillo, MM, Hamshere, ML, Pahwa, JS, Lupton, MK, Rubinsztein, DC, Brown, KS, Passmore, PA, McGuinness, B, Smith, AD, Kehoe, PG, Hooper, NM, Vardy, ERLC, Fox, NC, Goate, AM, Kauwe, JSK, Morris, JC, De Deyn, PP, Bass, NJ, McQuillin, A, Shaw, CE, Singleton, AB, Mühleisen, TW, Nöthen, MM, Pankratz, VS, Sando, SB, Aasly, JO, Wszolek, ZK, Dickson, DW, Graff Radford, NR, Petersen, RC, van Duijn, CM, Breteler, MMB, Ikram, MA, DeStefano, AL, Fitzpatrick, AL, Launer, LJ, Feulner, TM, Jonsson, PV, Bullido, MJ, ANNONI, GIORGIO, Holmans, PA, Younkin, SG, Owen, MJ, Williams, J., Hollingworth, P, Harold, D, Sims, R, Gerrish, A, Lambert, J, Carrasquillo, M, Abraham, R, Hamshere, M, Pahwa, J, Moskvina, V, Dowzell, K, Jones, N, Stretton, A, Thomas, C, Richards, A, Ivanov, D, Widdowson, C, Chapman, J, Lovestone, S, Powell, J, Proitsi, P, Lupton, M, Brayne, C, Rubinsztein, D, Gill, M, Lawlor, B, Lynch, A, Brown, K, Passmore, P, Craig, D, Mcguinness, B, Todd, S, Holmes, C, Mann, D, Smith, A, Beaumont, H, Warden, D, Wilcock, G, Love, S, Kehoe, P, Hooper, N, Vardy, E, Hardy, J, Mead, S, Fox, N, Rossor, M, Collinge, J, Maier, W, Jessen, F, Rüther, E, Schürmann, B, Heun, R, Kölsch, H, van den Bussche, H, Heuser, I, Kornhuber, J, Wiltfang, J, Dichgans, M, Frölich, L, Hampel, H, Gallacher, J, Hüll, M, Rujescu, D, Giegling, I, Goate, A, Kauwe, J, Cruchaga, C, Nowotny, P, Morris, J, Mayo, K, Sleegers, K, Bettens, K, Engelborghs, S, De Deyn, P, Van Broeckhoven, C, Livingston, G, Bass, N, Gurling, H, Mcquillin, A, Gwilliam, R, Deloukas, P, Al Chalabi, A, Shaw, C, Tsolaki, M, Singleton, A, Guerreiro, R, Mühleisen, T, Nöthen, M, Moebus, S, Jöckel, K, Klopp, N, Wichmann, H, Pankratz, V, Sando, S, Aasly, J, Barcikowska, M, Wszolek, Z, Dickson, D, Graff Radford, N, Petersen, R, van Duijn, C, Breteler, M, Ikram, M, Destefano, A, Fitzpatrick, A, Lopez, O, Launer, L, Seshadri, S, Berr, C, Campion, D, Epelbaum, J, Dartigues, J, Tzourio, C, Alpérovitch, A, Lathrop, M, Feulner, T, Friedrich, P, Riehle, C, Krawczak, M, Schreiber, S, Mayhaus, M, Nicolhaus, S, Wagenpfeil, S, Steinberg, S, Stefansson, H, Stefansson, K, Snædal, J, Björnsson, S, Jonsson, P, Chouraki, V, Genier Boley, B, Hiltunen, M, Soininen, H, Combarros, O, Zelenika, D, Delepine, M, Bullido, M, Pasquier, F, Mateo, I, Frank Garcia, A, Porcellini, E, Hanon, O, Coto, E, Alvarez, V, Bosco, P, Siciliano, G, Mancuso, M, Panza, F, Solfrizzi, V, Nacmias, B, Sorbi, S, Bossù, P, Piccardi, P, Arosio, B, Annoni, G, Seripa, D, Pilotto, A, Scarpini, E, Galimberti, D, Brice, A, Hannequin, D, Licastro, F, Jones, L, Holmans, P, Jonsson, T, Riemenschneider, M, Morgan, K, Younkin, S, Owen, M, O'Donovan, M, Amouyel, P, Williams, J, Carrasquillo, MM, Hamshere, ML, Pahwa, JS, Lupton, MK, Rubinsztein, DC, Brown, KS, Passmore, PA, McGuinness, B, Smith, AD, Kehoe, PG, Hooper, NM, Vardy, ERLC, Fox, NC, Goate, AM, Kauwe, JSK, Morris, JC, De Deyn, PP, Bass, NJ, McQuillin, A, Shaw, CE, Singleton, AB, Mühleisen, TW, Nöthen, MM, Pankratz, VS, Sando, SB, Aasly, JO, Wszolek, ZK, Dickson, DW, Graff Radford, NR, Petersen, RC, van Duijn, CM, Breteler, MMB, Ikram, MA, DeStefano, AL, Fitzpatrick, AL, Launer, LJ, Feulner, TM, Jonsson, PV, Bullido, MJ, ANNONI, GIORGIO, Holmans, PA, Younkin, SG, Owen, MJ, and Williams, J.

Abstract

We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ĝ‰Currency sign 1 × 10 -5. We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10 -17; including ADGC data, meta P = 5.0 × 10 -21) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10 -14; including ADGC data, meta P = 1.2 × 10 -16) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10 -4; including ADGC data, meta P = 8.6 × 10 -9), CD33 (GERAD+, P = 2.2 × 10 -4; including ADGC data, meta P = 1.6 × 10 -9) and EPHA1 (GERAD+, P = 3.4 × 10 -4; including ADGC data, meta P = 6.0 × 10 -10). © 2011 Nature America, Inc. All rights reserved.

Published
2011

33. Homocysteine and folate as risk factors for dementia and Alzheimer disease.

Author

Ravaglia G, Forti P, Maioli F, Martelli M, Servadei L, Brunetti N, Porcellini E, and Licastro F

Abstract

BACKGROUND: In cross-sectional studies, elevated plasma total homocysteine (tHcy) concentrations have been associated with cognitive impairment and dementia. Incidence studies of this issue are few and have produced conflicting results. OBJECTIVE: We investigated the relation between high plasma tHcy concentrations and risk of dementia and Alzheimer disease (AD) in an elderly population. DESIGN: A dementia-free cohort of 816 subjects (434 women and 382 men; mean age: 74 y) from an Italian population-based study constituted our study sample. The relation of baseline plasma tHcy to the risk of newly diagnosed dementia and AD on follow-up was examined. A proportional hazards regression model was used to adjust for age, sex, education, apolipoprotein E genotype, vascular risk factors, and serum concentrations of folate and vitamin B-12. RESULTS: Over an average follow-up of 4 y, dementia developed in 112 subjects, including 70 who received a diagnosis of AD. In the subjects with hyperhomocysteinemia (plasma tHcy > 15 mumol/L), the hazard ratio for dementia was 2.08 (95% CI: 1.31, 3.30; P = 0.002). The corresponding hazard ratio for AD was 2.11 (95% CI: 1.19, 3.76; P = 0.011). Independently of hyperhomocysteinemia and other confounders, low folate concentrations (

Published
2005

34. Elevated Plasma Levels of -1-Anti-Chymotrypsin in Age-Related Cognitive Decline and Alzheimers Disease: A Potential Therapeutic Target

Author

Porcellini, E., Davis, E., Chiappelli, M., Ianni, E., Di Stefano, G., Forti, P., Ravaglia, G., and Licastro, F.

Abstract

-1-antichymotrypsin (ACT), is an acute phase protein and a protease inhibitor produced by the liver and brain. ACT is involved in the pathogenesis of Alzheimers disease (AD), since elevated ACT concentration was found in cerebrospinal fluid (CSF) and brain from AD. ACT has also been shown to influence amyloid deposition in vitro and in animal models of AD. In this investigation 830 healthy controls, 69 subjects with cognitive impairment and not dementia (CIND), 53 patients with severe clinical AD and 142 patients with mild AD were investigated. Plasma levels of ACT were measured with a new competitive immune enzyme linked immune-assay (ELISA). ACT levels were higher in AD patients than in CIND or controls. An age dependent increase of plasma ACT was present in both healthy elderly and CIND. Patients with mild clinical AD were followed up for two years and stratified according to the rate of clinical deterioration. CT plasma levels were elevated in AD patients that showed an accelerated rate of cognitive deterioration during the follow up; this increment being prominent in AD with the Apolipoprotein E (APOE) 4 allele. Therefore, increased peripheral ACT levels in APOE 4 positive patients appear to predict an accelerated clinical progression. Plasma ACT might be used as a surrogate marker to monitor the conversion of pre-dementia stages to AD and the progression of the disease. The development of compounds able to interfere with the ACT biological activity (protease inhibition and/or promotion of amyloid deposition) might have therapeutic relevance for the disease.

Published
2008

36. Serum neutrophil gelatinase-B associated lipocalin (NGAL) levels in Down’s syndrome patients

Author

Porcellini Elisa, Licastro Federico, Galliera Emanuela, Dogliotti Giada, and Corsi Massimiliano M

Subjects
Immunologic diseases. Allergy, RC581-607, Geriatrics, RC952-954.6
Abstract

Abstract Neutrophil gelatinase-associated lipocalin (NGAL) is a group of proteins with different functions. NGAL is released by different cell types such as epithelial cell, hepatocytes and renal tubular cells during inflammation and after cell injury. Expression of NGAL is induced under various pathophysiological conditions such as infection, cancer, inflammation, kidney injury, cardiovascular disease, burn injury, and intoxication, which has an important anti-apoptotic and anti-inflammatory role. Subjects with Down’s syndrome (DS) are affected by many pathological age related conditions such as mental retardation, Alzheimer’s disease, immune defects and increased susceptibility to infections. The aim of this study is to evaluate possible use of NGAL as a marker of inflammatory status for allow an early diagnosis of inflammatory disease such as autoimmune disease in DS patients, that are more susceptible to these pathologies, especially in elderly subjects. In this study were recruited 3 groups of DS subjects (children, adults and elderly) and compared them to healthy control group. The molecules of interest was determinated by immuno-enzymatic assay (ELISA). Our results show that NGAL plasmatic level was significantly higher in DS patients compared to healthy controls. Moreover NGAL levels increase in correlation with the age, and showed a significantly correlation between the increase with the severity of disease. DS is characterized by an enhancement of gene production such as GART, SOD-1 and CBS that encode specific protein and enzyme involved in hydrogen peroxide and superoxide production, species highly cytotoxic implicated in inflammation and ageing. NGAL may have the potential application to ameliorate the toxicity induced by oxidative stress conditions such as Alzheimer’s disease, thalassemia, cardiovascular disease, burn injury, transplantation, diabetes, and aging.

Published
2010
Full Text
View/download PDF

37. Altered glycosylation profile of purified plasma ACT from Alzheimer’s disease

Author

Carbone Ilaria, Chiappelli Martina, Porcellini Elisa, Di Stefano Giuseppina, Manerba Marcella, Ianni Manuela, and Licastro Federico

Subjects
Immunologic diseases. Allergy, RC581-607, Geriatrics, RC952-954.6
Abstract

Abstract Background Alzheimer’s disease (AD) is one of the most frequent cause of neurodegenerative disorder in the elderly. Inflammation has been implicated in brain degenerative processes and peripheral markers of brain AD related impairment would be useful. Plasma levels of alpha-1-antichymotrypsin (ACT), an acute phase protein and a secondary component of amyloid plaques, are often increased in AD patients and high blood ACT levels correlate with progressive cognitive deterioration. During inflammatory responses changes in the micro-heterogeneity of ACT sugar chains have been described. Methods N-Glycanase digestion from Flavobacterium meningosepticum (PNGase F) was performed on both native and denatured purified ACT condition and resolved to Western blot with the purpose to revealed the ACT de-glycosylation pattern. Further characterization of the ACT glycan profile was obtained by a glycoarray; each lectin group in the assay specifically recognizes one or two glycans/epitopes. Lectin-bound ACT produced a glyco-fingerprint and mayor differences between AD and controls samples were assessed by a specific algorithms. Results Western blot analysis of purified ACT after PNGase F treatment and analysis of sugar composition of ACT showed significantly difference in “glyco-fingerprints” patterns from controls (CTR) and AD; ACT from AD showing significantly reduced levels of sialic acid. A difference in terminal GlcNac residues appeared to be related with progressive cognitive deterioration. Conclusions Low content of terminal GlcNac and sialic acid in peripheral ACT in AD patients suggests that a different pattern of glycosylation might be a marker of brain inflammation. Moreover ACT glycosylation analysis could be used to predict AD clinical progression and used in clinical trials as surrogate marker of clinical efficacy.

Published
2010
Full Text
View/download PDF

38. Multi factorial interactions in the pathogenesis pathway of Alzheimer’s disease: a new risk charts for prevention of dementia

Author

Carbone Ilaria, Buscema Massimo, Forti Paola, Porcellini Elisa, Licastro Federico, Ravaglia Giovanni, and Grossi Enzo

Subjects
Immunologic diseases. Allergy, RC581-607, Geriatrics, RC952-954.6
Abstract

Abstract Background The population longitudinal study named “The Conselice Study” has been the focus of the present investigation. 65 years old or older participants of this population study on brain aging were followed up for 5 years: 937 subjects completed the follow-up. Relationships of 46 genetic, phenotypic, clinical and nutritional factors on incident cognitive decline and incident dementia cases were investigated. Results A new statistical approach, called the Auto Contractive Map (AutoCM) was applied to find relationship between variables and a possible hierarchy in the relevance of each variable with incident dementia. This method, based on an artificial adaptive system, was able to define the association strength of each variable with all the others. Moreover, few variables resulted to be aggregation points in the variable connectivity map related to cognitive decline and dementia. Gene variants and cognate phenotypic variables showed differential degrees of relevance to brain aging and dementia. A risk map for age associated cognitive decline and dementia has been constructed and will be presented and discussed. Conclusion This map of variables may be use to identify subjects with increased risk of developing cognitive decline end/or dementia and provide pivotal information for early intervention protocols for prevention of dementia.

Published
2010
Full Text
View/download PDF

39. Pro-inflammatory genetic profile and familiarity of acute myocardial infarction

Author

Ianni Manuela, Callegari Sergio, Rizzo Antonio, Pastori Paolo, Moruzzi Paolo, Corradi Domenico, Porcellini Elisa, Campo Gianluca, Ferrari Roberto, Ferrario Marco M, Bitonte Stefania, Carbone Ilaria, and Licastro Federico

Subjects
Acute myocardial infarction, Family history, Genetic association, Inflammation, Immunologic diseases. Allergy, RC581-607, Geriatrics, RC952-954.6
Abstract

Abstract Background Acute myocardial infarction (AMI) is a multifactorial disease with a complex pathogenesis where lifestyle, individual genetic background and environmental risk factors are involved. Altered inflammatory responses are implicated in the pathogenesis of atherosclerosis and a premature AMI of parents is associated with an increased risk of the disease in their offspring (Offs). However, the genetic background of familiarity for AMI is still largely unknown. To understand which genes may predispose to increased risk of cardiovascular disease gene polymorphism of immune regulatory genes, and clinical events from the Offs of parents with an early AMI were investigated. Genetics data from Offs were compared with those obtained from healthy subjects and an independent cohort of patients with clinical sporadic AMI. Rates of clinical events during a 24 years follow up from Offs and from an independent Italian population survey were also evaluated. Results This study showed that a genetic signature consisting of the concomitant presence of the CC genotype of VEGF, the A allele of IL-10 and the A allele of IFN-γ was indeed present in the Offs population. In fact, the above genetic markers were more frequent in unaffected Offs (46.4%) and patients with sporadic AMI (31.8%) than in the CTR (17.3%) and the differences were highly statistically significant (Offs vs CTR: p = 0.0001, OR = 4.129; AMI vs CTR: p = 0.0001, OR = 2.224). During the 24-year follow-up, Offs with a positive familiarity in spite of a relatively young age showed an increased prevalence of diabetes, ischemic heart disease and stroke. These findings reinforce the notion that subjects with a familial history of AMI are at risk of an accelerated aging of cardiovascular system resulting in cardiovascular events. Conclusion Our data suggest that selected genes with immune regulatory functions are part of the complex genetic background contributing to familiarity for cardiovascular diseases. This inflammatory genetic profile, along with classical cardiovascular risk factors, may be used for better defining individual risk of AMI in unaffected subjects.

Published
2012
Full Text
View/download PDF

40. Alzheimer's disease gene signature says: beware of brain viral infections

Author

Ianni Manuela, Carbone Ilaria, Porcellini Elisa, and Licastro Federico

Subjects
Immunologic diseases. Allergy, RC581-607, Geriatrics, RC952-954.6
Abstract

Abstract Background Recent findings from a genome wide association investigation in a large cohort of patients with Alzheimer's disease (AD) and non demented controls (CTR) showed that a limited set of genes was in a strong association (p > l0-5) with the disease. Presentation of the hypothesis In this report we suggest that the polymorphism association in 8 of these genes is consistent with a non conventional interpretation of AD etiology. Nectin-2 (NC-2), apolipoprotein E (APOE), glycoprotein carcinoembryonic antigen related cell adhesion molecule- 16 (CEACAM-16), B-cell lymphoma-3 (Bcl-3), translocase of outer mitochondrial membrane 40 homolog (T0MM-40), complement receptor-1 (CR-l), APOJ or clusterin and C-type lectin domain A family-16 member (CLEC-16A) result in a genetic signature that might affect individual brain susceptibility to infection by herpes virus family during aging, leading to neuronal loss, inflammation and amyloid deposition. Implications of the hypothesis We hypothesized that such genetic trait may predispose to AD via complex and diverse mechanisms each contributing to an increase of individual susceptibility to brain viral infections

Published
2010
Full Text
View/download PDF

41. Innate immunity and inflammation in ageing: a key for understanding age-related diseases

Author

Colonna-Romano Giuseppina, Porcellini Elisa, Lio Domenico, Candore Giuseppina, Licastro Federico, Franceschi Claudio, and Caruso Calogero

Subjects
Age-related diseases, Cytokine, Inflammation, Innate Immunity, Longevity, Immunologic diseases. Allergy, RC581-607, Geriatrics, RC952-954.6
Abstract

Abstract The process of maintaining life for the individual is a constant struggle to preserve his/her integrity. This can come at a price when immunity is involved, namely systemic inflammation. Inflammation is not per se a negative phenomenon: it is the response of the immune system to the invasion of viruses or bacteria and other pathogens. During evolution the human organism was set to live 40 or 50 years; today, however, the immune system must remain active for much a longer time. This very long activity leads to a chronic inflammation that slowly but inexorably damages one or several organs: this is a typical phenomenon linked to ageing and it is considered the major risk factor for age-related chronic diseases. Alzheimer's disease, atherosclerosis, diabetes and even sarcopenia and cancer, just to mention a few – have an important inflammatory component, though disease progression seems also dependent on the genetic background of individuals. Emerging evidence suggests that pro-inflammatory genotypes are related to unsuccessful ageing, and, reciprocally, controlling inflammatory status may allow a better chance of successful ageing. In other words, age-related diseases are "the price we pay" for a life-long active immune system: this system has also the potential to harm us later, as its fine tuning becomes compromised. Our immune system has evolved to control pathogens, so pro-inflammatory responses are likely to be evolutionarily programmed to resist fatal infections with pathogens aggressively. Thus, inflammatory genotypes are an important and necessary part of the normal host responses to pathogens in early life, but the overproduction of inflammatory molecules might also cause immune-related inflammatory diseases and eventually death later. Therefore, low responder genotypes involved in regulation of innate defence mechanisms, might better control inflammatory responses and age-related disease development, resulting in an increased chance of long life survival in a "permissive" environment with reduced pathogen load, medical care and increased quality of life.

Published
2005
Full Text
View/download PDF

42. SHIP2: A 'NEW' Insulin Pathway Target for Aging Research

Author

VastoSonya, VergaSalvatore, EmanueleFabrizio, PorcelliniElisa, CarusoCalogero, BalistreriCarmela Rita, CandoreGiuseppina, MonasteroRoberto, AccardiGiulia, LicastroFederico, VirrusoClaudia, Accardi, G, Virruso, C, Balistreri, CR, Emanuele, F, Licastro, F, Monastero, R, Porcellini, E, Vasto, S, Verga, S, Caruso, C, Candore, G, Accardi G, Virruso C, Balistreri CR, Emanuele F, Licastro F, Monastero R, Porcellini E, Vasto S, Verga S, Caruso C, and Candore G

Subjects
Adult, Aging, medicine.medical_specialty, medicine.medical_treatment, Disease, Biology, Systemic inflammation, Polymorphism, Single Nucleotide, polymorphism, chemistry.chemical_compound, domain-containing inositol 5-phosphatase 2 (SHIP2), insulin-like growth factor I (IGF-I), type 2 diabetes mellitus (T2DM), INFLAMMATION, Gene Frequency, Alzheimer Disease, Diabetes mellitus, Internal medicine, medicine, Humans, Insulin, Settore MED/05 - Patologia Clinica, SNP, Inositol, Aged, Settore MED/04 - Patologia Generale, ALZHEIMER’S DISEASE, Research, Inositol Polyphosphate 5-Phosphatases, NEURODEGENERATION, Type 2 Diabetes Mellitus, medicine.disease, Phosphoric Monoester Hydrolases, Endocrinology, Diabetes Mellitus, Type 2, chemistry, Immunology, Settore MED/26 - Neurologia, Geriatrics and Gerontology, medicine.symptom, Metabolic syndrome, Signal Transduction
Abstract

Strong evidence suggests that systemic inflammation and central adiposity contribute to and perpetuate metabolic syndrome. All of these alterations predispose individuals to type 2 diabetes mellitus (T2DM), cardiovascular disease, as well as Alzheimer's disease (AD), all characterized by chronic inflammatory status. On the other hand, extensive abnormalities in insulin and insulin-like growth factor I (IGF-I) and IGF-II signaling mechanisms in brains with AD have been demonstrated, suggesting that AD could be a third form of diabetes. The Src homology domain-containing inositol 5-phosphatase 2 (SHIP2) has an important role in the insulin pathway because its over-expression causes impairment of insulin/IGF-1 signaling. Because some single-nucleotide polymorphisms (SNP) of the gene encoding SHIP2 were significantly associated in T2DM patients with metabolic syndrome and some related conditions, we decided to conduct a case-control study on this gene, analyzing AD and T2DM subjects as cases and young, old, and centenarians as controls. Our results suggest a putative correlation between the the rs144989913 SNP and aging, both successful and unsuccessful, rather than age-related diseases. Because this SNP is an insertion/deletion of 28 bp, it might cause an alteration in SHIP2 expression. It is noteworthy that SHIP2 has been demonstrated to be a potent negative regulator of insulin signaling and insulin sensitivity. Many studies demonstrated the association of the insulin/IGF1 pathway with aging and longevity, so it is tempting to speculate that the found association with SHIP2 and aging might depend on its effect on the insulin/IGF-1 pathway.

Published
2014

43. Common Variants at Abca7, Ms4A6A/Ms4A4E, Epha1, Cd33 and Cd2Ap Are Associated with Alzheimer'S Disease

Author

Neill R. Graff-Radford, Caroline S. Widdowson, John Hardy, Simon Lovestone, Stefan Schreiber, Ana Frank-García, Amy Gerrish, Kevin Mayo, Alexandra Stretton, Michael John Owen, Minerva M. Carrasquillo, Seth Love, Jade Chapman, Vincent Chouraki, Monique M.B. Breteler, Francesco Panza, Emma R L C Vardy, Ronald C. Petersen, Harald Hampel, S. Nicolhaus, Lenore J. Launer, Michelle K. Lupton, Eckart Rüther, A. David Smith, David C. Rubinsztein, Rebecca Sims, Gill Livingston, Diana Zelenika, Simon Mead, Martin N. Rossor, Hilkka Soininen, Christine Van Broeckhoven, Kristel Sleegers, Thorlakur Jonsson, M. Arfan Ikram, Helen Beaumont, Michael Conlon O'Donovan, Federico Licastro, Sudha Seshadri, Alexander Richards, Nick C. Fox, Markus M. Nöthen, Claudine Berr, T. Feulner, Benedetta Nacmias, Carlos Cruchaga, Peter Passmore, Oscar L. Lopez, Julie Williams, Matthias Riemenschneider, Florence Pasquier, John Gallacher, Didier Hannequin, Sigrid Botne Sando, Jens Wiltfang, Charlene Thomas, Gabriele Siciliano, Maria Barcikowska, Mikko Hiltunen, Carol Brayne, Dobril Ivanov, Anita L. DeStefano, Bernadette McGuinness, Norman Klopp, Gordon K. Wilcock, Aoibhinn Lynch, Wolfgang Maier, Peter Holmans, H.-Erich Wichmann, Giorgio Annoni, Beatrice Arosio, Alison Goate, Sigurbjorn Bjornsson, Karl-Heinz Jöckel, Dan Rujescu, Hugh Gurling, Nigel M. Hooper, Clive Holmes, Andrew McQuillin, Patricia Friedrich, John Powell, Rhian Gwilliam, R. Heun, Jacques Epelbaum, Isabella Heuser, Magda Tsolaki, Dennis W. Dickson, Alberto Pilotto, Stephen Todd, Dominique Campion, Michael Krawczak, Jan O. Aasly, Olivier Hanon, Patrick G. Kehoe, Johannes Kornhuber, Marc Delepine, Peter Paul De Deyn, Britta Schürmann, Brian A. Lawlor, Christophe Tzourio, Richard Abraham, Petra Nowotny, Jean-François Dartigues, Heike Kölsch, Michelangelo Mancuso, Marian L. Hamshere, Zbigniew K. Wszolek, Paola Piccardi, Paolo Bosco, Jean-Charles Lambert, Denise Harold, Frank Jessen, Palmi V. Jonsson, Paola Bossù, Paul Hollingworth, Jon Snaedal, Michael Gill, Onofre Combarros, David M. A. Mann, John C. Morris, Annette L. Fitzpatrick, Christopher Shaw, Alexis Brice, Philippe Amouyel, Elio Scarpini, Lesley Jones, Sebastiaan Engelborghs, Daniela Galimberti, Vincenzo Solfrizzi, V. Shane Pankratz, John Collinge, María J. Bullido, Kristelle Brown, Nicholas Bass, Andrew B. Singleton, Jaspreet Singh Pahwa, Kari Stefansson, Lutz Frölich, Steven G. Younkin, Ignacio Mateo, Annick Alpérovitch, Benjamin Genier-Boley, Ina Giegling, Caterina Riehle, Kimberley Dowzell, Mark Lathrop, Hreinn Stefansson, Sandro Sorbi, Rita Guerreiro, Thomas W. Mühleisen, Karolien Bettens, Michael Hüll, Martin Dichgans, Petroula Proitsi, Panagiotis Deloukas, Valentina Moskvina, Cornelia M. van Duijn, Donald Warden, Victoria Alvarez, Eliecer Coto, Kevin Morgan, Susanne Moebus, Ammar Al-Chalabi, Elisa Porcellini, Stefan Wagenpfeil, Hendrik van den Bussche, John S. K. Kauwe, Stacy Steinberg, David Craig, Nicola Jones, Manuel Mayhaus, Davide Seripa, Neurology, NCA - Neurodegeneration, HOLLINGWORTH P, HAROLD D, SIMS R, GERRISH A, LAMBERT JC, CARRASQUILLO MM, ABRAHAM R, HAMSHERE ML, PAHWA JS, MOSKVINA V, DOWZELL K, JONES N, STRETTON A, THOMAS C, RICHARDS A, IVANOV D, WIDDOWSON C, CHAPMAN J, LOVESTONE S, POWELL J, PROITSI P, LUPTON MK, BRAYNE C, RUBINSZTEIN DC, GILL M, LAWLOR B, LYNCH A, BROWN KS, PASSMORE PA, CRAIG D, MCGUINNESS B, TODD S, HOLMES C, MANN D, SMITH AD, BEAUMONT H, WARDEN D, WILCOCK G, LOVE S, KEHOE PG, HOOPER NM, VARDY ER, HARDY J, MEAD S, FOX NC, ROSSOR M, COLLINGE J, MAIER W, JESSEN F, RÜTHER E, SCHÜRMANN B, HEUN R, KÖLSCH H, VAN DEN BUSSCHE H, HEUSER I, KORNHUBER J, WILTFANG J, DICHGANS M, FRÖLICH L, HAMPEL H, GALLACHER J, HÜLL M, RUJESCU D, GIEGLING I, GOATE AM, KAUWE JS, CRUCHAGA C, NOWOTNY P, MORRIS JC, MAYO K, SLEEGERS K, BETTENS K, ENGELBORGHS S, DE DEYN PP, VAN BROECKHOVEN C, LIVINGSTON G, BASS NJ, GURLING H, MCQUILLIN A, GWILLIAM R, DELOUKAS P, AL-CHALABI A, SHAW CE, TSOLAKI M, SINGLETON AB, GUERREIRO R, MÜHLEISEN TW, NÖTHEN MM, MOEBUS S, JÖCKEL KH, KLOPP N, WICHMANN HE, PANKRATZ VS, SANDO SB, AASLY JO, BARCIKOWSKA M, WSZOLEK ZK, DICKSON DW, GRAFF-RADFORD NR, PETERSEN RC, ALZHEIMER'S DISEASE NEUROIMAGING INITIATIVE, VAN DUIJN CM, BRETELER MM, IKRAM MA, DESTEFANO AL, FITZPATRICK AL, LOPEZ O, LAUNER LJ, SESHADRI S, CHARGE CONSORTIUM, BERR C, CAMPION D, EPELBAUM J, DARTIGUES JF, TZOURIO C, ALPÉROVITCH A, LATHROP M, EADI1 CONSORTIUM, FEULNER TM, FRIEDRICH P, RIEHLE C, KRAWCZAK M, SCHREIBER S, MAYHAUS M, NICOLHAUS S, WAGENPFEIL S, STEINBERG S, STEFANSSON H, STEFANSSON K, SNAEDAL J, BJÖRNSSON S, JONSSON PV, CHOURAKI V, GENIER-BOLEY B, HILTUNEN M, SOININEN H, COMBARROS O, ZELENIKA D, DELEPINE M, BULLIDO MJ, PASQUIER F, MATEO I, FRANK-GARCIA A, PORCELLINI E, HANON O, COTO E, ALVAREZ V, BOSCO P, SICILIANO G, MANCUSO M, PANZA F, SOLFRIZZI V, NACMIAS B, SORBI S, BOSSÙ P, PICCARDI P, AROSIO B, ANNONI G, SERIPA D, PILOTTO A, SCARPINI E, GALIMBERTI D, BRICE A, HANNEQUIN D, LICASTRO F, JONES L, HOLMANS PA, JONSSON T, RIEMENSCHNEIDER M, MORGAN K, YOUNKIN SG, OWEN MJ, O'DONOVAN M, AMOUYEL P, WILLIAMS J, Epidemiology, Radiology & Nuclear Medicine, Clinical sciences, Pathologic Biochemistry and Physiology, Hollingworth, P, Harold, D, Sims, R, Gerrish, A, Lambert, J, Carrasquillo, M, Abraham, R, Hamshere, M, Pahwa, J, Moskvina, V, Dowzell, K, Jones, N, Stretton, A, Thomas, C, Richards, A, Ivanov, D, Widdowson, C, Chapman, J, Lovestone, S, Powell, J, Proitsi, P, Lupton, M, Brayne, C, Rubinsztein, D, Gill, M, Lawlor, B, Lynch, A, Brown, K, Passmore, P, Craig, D, Mcguinness, B, Todd, S, Holmes, C, Mann, D, Smith, A, Beaumont, H, Warden, D, Wilcock, G, Love, S, Kehoe, P, Hooper, N, Vardy, E, Hardy, J, Mead, S, Fox, N, Rossor, M, Collinge, J, Maier, W, Jessen, F, Rüther, E, Schürmann, B, Heun, R, Kölsch, H, van den Bussche, H, Heuser, I, Kornhuber, J, Wiltfang, J, Dichgans, M, Frölich, L, Hampel, H, Gallacher, J, Hüll, M, Rujescu, D, Giegling, I, Goate, A, Kauwe, J, Cruchaga, C, Nowotny, P, Morris, J, Mayo, K, Sleegers, K, Bettens, K, Engelborghs, S, De Deyn, P, Van Broeckhoven, C, Livingston, G, Bass, N, Gurling, H, Mcquillin, A, Gwilliam, R, Deloukas, P, Al Chalabi, A, Shaw, C, Tsolaki, M, Singleton, A, Guerreiro, R, Mühleisen, T, Nöthen, M, Moebus, S, Jöckel, K, Klopp, N, Wichmann, H, Pankratz, V, Sando, S, Aasly, J, Barcikowska, M, Wszolek, Z, Dickson, D, Graff Radford, N, Petersen, R, van Duijn, C, Breteler, M, Ikram, M, Destefano, A, Fitzpatrick, A, Lopez, O, Launer, L, Seshadri, S, Berr, C, Campion, D, Epelbaum, J, Dartigues, J, Tzourio, C, Alpérovitch, A, Lathrop, M, Feulner, T, Friedrich, P, Riehle, C, Krawczak, M, Schreiber, S, Mayhaus, M, Nicolhaus, S, Wagenpfeil, S, Steinberg, S, Stefansson, H, Stefansson, K, Snædal, J, Björnsson, S, Jonsson, P, Chouraki, V, Genier Boley, B, Hiltunen, M, Soininen, H, Combarros, O, Zelenika, D, Delepine, M, Bullido, M, Pasquier, F, Mateo, I, Frank Garcia, A, Porcellini, E, Hanon, O, Coto, E, Alvarez, V, Bosco, P, Siciliano, G, Mancuso, M, Panza, F, Solfrizzi, V, Nacmias, B, Sorbi, S, Bossù, P, Piccardi, P, Arosio, B, Annoni, G, Seripa, D, Pilotto, A, Scarpini, E, Galimberti, D, Brice, A, Hannequin, D, Licastro, F, Jones, L, Holmans, P, Jonsson, T, Riemenschneider, M, Morgan, K, Younkin, S, Owen, M, O'Donovan, M, Amouyel, P, and Williams, J

Subjects
Male, ABCA7 protein, human, ATP-Binding Cassette Transporters/genetics, Sialic Acid Binding Ig-like Lectin 3, CD33, SORL1, Medizin, genetics [Alzheimer Disease], Adaptor Proteins, Signal Transducing/genetics, Disease, PICALM, ABCA7, Disease susceptibility, 0302 clinical medicine, genetics [Adaptor Proteins, Signal Transducing], Databases, Genetic, GWAS, GENE-EXPRESSION, Medicine(all), Aged, 80 and over, Genetics, 0303 health sciences, Alzheimer's disease, genetic predisposition, Receptor, EphA1, ALZHEIMER’S DISEASE, Antigens, CD/genetics, genetics [Receptor, EphA1], genetics [Membrane Proteins], Multigene Family, Female, genetics [Antigens, Differentiation, Myelomonocytic], APOE, Antigens, Differentiation, Myelomonocytic, Single-nucleotide polymorphism, Case-control studies, Cytoskeletal Proteins/genetics, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, CD33 protein, human, Alzheimer Disease, Antigens, CD, ddc:570, Humans, Genetic Predisposition to Disease, Membrane Proteins/genetics, CLUSTERIN, Aged, genetics [Cytoskeletal Proteins], Adaptor Proteins, Signal Transducing, 030304 developmental biology, Alzheimer Disease/genetics, Antigens, Differentiation, Myelomonocytic/genetics, Genetic Variation, Membrane Proteins, CD2-associated protein, genetics [Antigens, CD], Cytoskeletal Proteins, MS4A4E protein, human, Case-Control Studies, Susceptibility locus, biology.protein, ATP-Binding Cassette Transporters, Human medicine, genetics [ATP-Binding Cassette Transporters], aged, 80 and over, Receptor, EphA1/genetics, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ĝ‰Currency sign 1 × 10 -5. We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10 -17; including ADGC data, meta P = 5.0 × 10 -21) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10 -14; including ADGC data, meta P = 1.2 × 10 -16) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10 -4; including ADGC data, meta P = 8.6 × 10 -9), CD33 (GERAD+, P = 2.2 × 10 -4; including ADGC data, meta P = 1.6 × 10 -9) and EPHA1 (GERAD+, P = 3.4 × 10 -4; including ADGC data, meta P = 6.0 × 10 -10). © 2011 Nature America, Inc. All rights reserved.

Published
2011

44. Sharing pathogenetic mechanisms between acute myocardial infarction and Alzheimer's disease as shown by partially overlapping of gene variant profiles

Author

Domenico Lio, Elizabeth H. Corder, Elisa Porcellini, Claudio Marcello Caldarera, Calogero Caruso, Martina Chiappelli, Federico Licastro, Ilaria Carbone, Licastro, F, Chiappelli, M, Caldarera, CM, Porcellini, E, Carbone, I, Caruso, C, Lio, D, Corder EH, Licastro F, Chiappelli M, Caldarera CM, Porcellini E, Carbone I, Caruso C, Lio D, and Corder EH.

Subjects
Apolipoprotein E, Adult, Male, Population, Myocardial Infarction, Disease, Alzheimer Disease, Risk Factors, Genes, Overlapping, Medicine, Humans, Settore MED/05 - Patologia Clinica, Genetic Predisposition to Disease, Myocardial infarction, Allele, education, genetic risk markers, common soil, alzheimer disease, AMI, GOM analysys, Gene, Aged, Genetics, Aged, 80 and over, education.field_of_study, business.industry, General Neuroscience, Gene Expression Profiling, Genetic Variation, General Medicine, Middle Aged, medicine.disease, Psychiatry and Mental health, Clinical Psychology, Relative risk, Immunology, Tumor necrosis factor alpha, Female, Geriatrics and Gerontology, business
Abstract

Gene variants that promote inflammation and cholesterol metabolism have been associated with acute myocardial infarction (AMI) and Alzheimer's disease (AD). We investigated a panel of relevant polymorphisms to distinguish genetic backgrounds for AMI and AD: IL10 -1082G/A, IL6 -174G/C, TNF -308G/A, IFNG +874T/A, SERPINA3 -51G/T, HMGCR -911C/A, APOE e2/3/4 (280 AMI cases, 257 AD cases, and 1307 population controls, all Italian (presumed risk alleles are shown in bold). Six genetic risk sets I to VI were identified by fuzzy latent classification: I had low risk; II and III had low risk before age 65 (II, III); low risk sets lacked pro-inflammatory alleles for HMGCR-TNF-APOE. Pro-inflammatory alleles for SERPINA3-IL10-IFNG were found for high risk sets IV to VI. Set IV 'AMI < age 40, AD < age 65' included risk alleles for HMGCR. Set V 'AMI over a broad range of age' included risk alleles for TNF+IL6. Set VI 'AMI at ages 40 to 55, AD ages 65+' included APOE e4. Close resemblance to the high risk sets, as indicated by membership scores close to one, defined high relative risks. We conclude that AMI and AD share genetic backgrounds involving cholesterol metabolism and the upregulation of inflammation and that gene-gene interactions in relevant sets of genes may be useful in defining inherited risk for common disorders.

Published
2011

45. Evidence of the association of BIN1 and PICALM with the AD risk in contrasting European populations

Author

Anne Boland, Giorgio Annoni, Elisa Porcellini, Gloria Tognoni, Giovanni Ravaglia, Mark Lathrop, Ignacio Mateo, Paola Bossù, Diana Zelenika, Nathalie Fievet, Marc Delepine, Mikko Hiltunen, Ana Frank-García, Hilkka Soininen, Paola Forti, Gianfranco Spalletta, Federico Licastro, Daniela Galimberti, Paola Piccardi, Maria Del Zompo, Seppo Helisalmi, Michelangelo Mancuso, Vincenzo Solfrizzi, Francesco Panza, Davide Seripa, Philippe Amouyel, María J. Bullido, Paolo Bosco, Gabriele Siciliano, Alberto Pilotto, Vincent Chouraki, Beatrice Arosio, Fernando Valdivieso, Jean-Charles Lambert, Elio Scarpini, Victoria Alvarez, Onofre Combarros, Sandro Sorbi, Benedetta Nacmias, Raffaele Ferri, Eliecer Coto, Lambert, J, Zelenika, D, Hiltunen, M, Chouraki, V, Combarros, O, Bullido, M, Tognoni, G, Fiévet, N, Boland, A, Arosio, B, Coto, E, Zompo, M, Mateo, I, Frank Garcia, A, Helisalmi, S, Porcellini, E, Pilotto, A, Forti, P, Ferri, R, Delepine, M, Scarpini, E, Siciliano, G, Solfrizzi, V, Sorbi, S, Spalletta, G, Ravaglia, G, Valdivieso, F, Alvarez, V, Bosco, P, Mancuso, M, Panza, F, Nacmias, B, Bossù, P, Piccardi, P, Annoni, G, Seripa, D, Galimberti, D, Licastro, F, Lathrop, M, Soininen, H, Amouyel, P, Lambert JC, Zelenika D, Hiltunen M, Chouraki V, Combarros O, Bullido MJ, Tognoni G, Fiévet N, Boland A, Arosio B, Coto E, Zompo MD, Mateo I, Frank-Garcia A, Helisalmi S, Porcellini E, Pilotto A, Forti P, Ferri R, Delepine M, Scarpini E, Siciliano G, Solfrizzi V, Sorbi S, Spalletta G, Ravaglia G, Valdivieso F, Alvarez V, Bosco P, Mancuso M, Panza F, Nacmias B, Bossù P, Piccardi P, Annoni G, Seripa D, Galimberti D, Licastro F, Lathrop M, Soininen H, Amouyel P, and Universidad de Cantabria

Subjects
Apolipoprotein E, Aging, BIN1, Genotype, Disease, Biology, GWA, Polymorphism, Single Nucleotide, White People, PICALM, Polymorphism (computer science), Alzheimer Disease, Humans, Genetic Predisposition to Disease, Finland, Genetic Association Studies, Genetic association, Adaptor Proteins, Signal Transducing, Genetics, ALZHEIMER’S DISEASE, General Neuroscience, Tumor Suppressor Proteins, Nuclear Proteins, Odds ratio, POLYMORPHISM, Confidence interval, Italy, Spain, Monomeric Clathrin Assembly Proteins, Neurology (clinical), BIN1, PICALM, EXOC3L2, APOE, Alzheimer, Risk, GWA, Association, Polymorphism, Geriatrics and Gerontology, APOE, Developmental Biology
Abstract

Recent genome-wide association studies have identified 5 loci (BIM, CLU, CR1, EXOC3L2, and PICALM) as genetic determinants of Alzheimer's disease (AD). We attempted to confirm the association between these genes and the AD risk in 3 contrasting European populations (from Finland, Italy, and Spain). Because CLU and CRI had already been analyzed in these populations, we restricted our investigation to BIN1, EXO2CL3, and PICALM. In a total of 2816 AD cases and 2706 controls, we unambiguously replicated the association of rs744373 (for BIN1) and rs541458 (for PICALM) polymorphisms with the AD risk (odds ratio [OR] = 1.26, 95% confidence interval [Cl] [1.15-1.38], p = 2.9 X 10(-7), and OR = 0.80, 95% CI [0.74-0.88], p = 4.6 X 10(-7), respectively). In a meta-analysis, rs597668 (EXOC3L2) was also associated with the AD risk, albeit to a lesser extent (OR = 1.19, 95% Cl [1.06-1.32], p = 2.0 X 10(-3)). However, this signal did not appear to be independent of APOE. In conclusion, we confirmed that BIN! and PICALM are genetic determinants of AD, whereas the potential involvement of EXOC3L2 requires further investigation. (C) 2011 Elsevier Inc. All rights reserved.

Published
2011

46. Role of prothrombotic polymorphisms in successful or unsuccessful aging

Author

Martina Chiappelli, Marisa Palmeri, Letizia Scola, Federico Licastro, Elisa Porcellini, Loredana Vaccarino, Domenico Lio, Calogero Caruso, Gabriella Misiano, Giusi Irma Forte, Vaccarino L, Forte GI, Palmeri M, Misiano G, Porcellini E, Chiappelli M, Scola L, Caruso C, Licastro F, Lio D., Vaccarino, L, Forte, GI, Palmeri, M, Misiano, G, Porcellini, E, Chiappelli, M, Scola, L, Caruso, C, Licastro, F, and Lio, D.

Subjects
Gerontology, Male, Aging, media_common.quotation_subject, Disease, Bioinformatics, Leiden factor V, Prothrombin, Nonagenarians, Alzheimer disease, Polymorphism (computer science), Alzheimer Disease, medicine, Dementia, Humans, Nonagenarian, Allele, Alleles, media_common, Aged, Settore MED/04 - Patologia Generale, Polymorphism, Genetic, Successful aging, business.industry, ALZHEIMER’S DISEASE, aging, Longevity, Factor V, medicine.disease, Case-Control Studies, Cohort, Female, Geriatrics and Gerontology, Alzheimer's disease, business, Leiden Factor V
Abstract

The study of the genetic profile of centenarians aims to identify the genes and allelic variants which may influence a greater life expectancy and that can be considered as predisposing factors associated to the aging diseases, such as Alzheimer. Centenarians, that represent a cohort of selected survivors, show an hypercoagulability state characterised by striking signs of high coagulation enzyme activity, as directly assessed by the tested higher plasma level of some important factors involved in the haemostasis balance. Anyway, these individuals seem to have a reduced susceptibility to dementia, as well as to cardiovascular events. In this study we analyze the frequencies of Leiden Factor V polymorphism (G1691A), and G20210A of prothrombin (FII) in three cohorts of subjects: patients with Alzheimer’s disease (unsuccessful aging), nonagenarians (successful aging) and young healthy controls, to assess whether allelic variants associated to the modification of haemostatic system function, may play a role in the protection or susceptibility to Alzheimer disease, as well as to reach a successful aging. No significant differences were observed in the frequencies of the three groups studied. These results indicate that the presence or absence of the gene variants examined did not influence the achievement of advanced age and are not risk factors for Alzheimer’s disease. The state of hypercoagulability and the possession of these risk alleles appear to be compatible with the achievement of longevity and are not implied as risk factors in Alzheimer disease development.

Published
2011

47. The CALHM1 P86L polymorphism is a genetic modifier of age at onset in Alzheimer's disease: a meta-analysis study

Author

Rudolph E. Tanzi, Dominique Campion, Brit Maren Michaud Schjeide, Diana Zelenika, Lars Lannfelt, Nathalie Fievet, Paola Forti, M. Ilyas Kamboh, Antonio González-Pérez, Hilkka Soininen, Elicer Coto, Steven T. DeKosky, Victoria Alvarez, Carmen Antúnez, Karolien Bettens, Margaret A. Pericak-Vance, Michelangelo Mancuso, Jacques Epelbaum, Kristel Sleegers, Federico Licastro, Giorgio Annoni, Florence Pasquier, Gianfranco Spalletta, Claudine Berr, Florence Richard, Christine Van Broeckhoven, Ana Frank-García, Lars Bertram, Mikko Hiltunen, Daniela Galimberti, Jean-Charles Lambert, Philippe Marambaud, Elisa Porcellini, Maria Del Zompo, Seppo Helisalmi, Nathalie Brouwers, Ignacio Mateo, Corinne Lendon, Gabriele Siciliano, David M. A. Mann, Fernando Valdivieso, Annick Alpérovitch, Jean-François Dartigues, Paola Piccardi, Jesús López-Arrieta, Alberto Pilotto, Mercè Boada, Olivier Hanon, Elio Scarpini, Vilmentas Giedraitis, Didier Hannequin, Benedetta Nacmias, Onofre Combarros, Giovanni Ravaglia, Mark Lathrop, Christophe Tzourio, Paola Bossù, María J. Bullido, Martin Ingelsson, Sandro Sorbi, Paolo Bosco, Philippe Amouyel, Vincenzo Solfrizzi, Sebastiaan Engelborghs, Beatrice Arosio, Francesco Panza, Marc Delepine, Saila Vepsäläinen, Jonathan L. Haines, Peter Paul De Deyn, Gary W. Beecham, Agustín Ruiz, Davide Seripa, Gloria Tognoni, Raffaele Ferri, Lambert JC, Sleegers K, González-Pérez A, Ingelsson M, Beecham GW, Hiltunen M, Combarros O, Bullido MJ, Brouwers N, Bettens K, Berr C, Pasquier F, Richard F, Dekosky ST, Hannequin D, Haines JL, Tognoni G, Fiévet N, Dartigues JF, Tzourio C, Engelborghs S, Arosio B, Coto E, De Deyn P, Del Zompo M, Mateo I, Boada M, Antunez C, Lopez-Arrieta J, Epelbaum J, Schjeide BM, Frank-Garcia A, Giedraitis V, Helisalmi S, Porcellini E, Pilotto A, Forti P, Ferri R, Delepine M, Zelenika D, Lathrop M, Scarpini E, Siciliano G, Solfrizzi V, Sorbi S, Spalletta G, Ravaglia G, Valdivieso F, Vepsäläinen S, Alvarez V, Bosco P, Mancuso M, Panza F, Nacmias B, Bossù P, Hanon O, Piccardi P, Annoni G, Mann D, Marambaud P, Seripa D, Galimberti D, Tanzi RE, Bertram L, Lendon C, Lannfelt L, Licastro F, Campion D, Pericak-Vance MA, Soininen H, Van Broeckhoven C, Alpérovitch A, Ruiz A, Kamboh MI, Amouyel P., Lambert, J, Sleegers, K, González Pérez, A, Ingelsson, M, Beecham, G, Hiltunen, M, Combarros, O, Bullido, M, Brouwers, N, Bettens, K, Berr, C, Pasquier, F, Richard, F, Dekosky, S, Hannequin, D, Haines, J, Tognoni, G, Fiévet, N, Dartigues, J, Tzourio, C, Engelborghs, S, Arosio, B, Coto, E, De Deyn, P, Del Zompo, M, Mateo, I, Boada, M, Antunez, C, Lopez Arrieta, J, Epelbaum, J, Schjeide, B, Frank Garcia, A, Giedraitis, V, Helisalmi, S, Porcellini, E, Pilotto, A, Forti, P, Ferri, R, Delepine, M, Zelenika, D, Lathrop, M, Scarpini, E, Siciliano, G, Solfrizzi, V, Sorbi, S, Spalletta, G, Ravaglia, G, Valdivieso, F, Vepsäläinen, S, Alvarez, V, Bosco, P, Mancuso, M, Panza, F, Nacmias, B, Bossù, P, Hanon, O, Piccardi, P, Annoni, G, Mann, D, Marambaud, P, Seripa, D, Galimberti, D, Tanzi, R, Bertram, L, Lendon, C, Lannfelt, L, Licastro, F, Campion, D, Pericak Vance, M, Soininen, H, Van Broeckhoven, C, Alpérovitch, A, Ruiz, A, Kamboh, M, Amouyel, P, Clinical sciences, and Neurology

Subjects
Apolipoprotein E, Male, CALHM1, Calcium Channels/genetics, Apolipoprotein E4, Single-nucleotide polymorphism, Biology, Article, polymorphism, Alzheimer Disease/epidemiology, Alzheimer Disease, Genetic variation, Genotype, Humans, Apolipoprotein E4/genetics, Allele, Age of Onset, Polymorphism, Genetic/genetics, Alleles, apolipoprotein E, Aged, Medicine(all), Genetics, Aged, 80 and over, Membrane Glycoproteins, Polymorphism, Genetic, General Neuroscience, Haplotype, Age at onset, General Medicine, Membrane Glycoproteins/genetics, Alzheimer's disease, Middle Aged, Psychiatry and Mental health, Clinical Psychology, Case-Control Studies, Female, Human medicine, Calcium Channels, Geriatrics and Gerontology, Age of onset
Abstract

The only established genetic determinant of non-Mendelian forms of Alzheimer's disease (AD) is the epsilon 4 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 epsilon 4 allele of the APOE gene.

Published
2010

48. Unraveling the role of microRNA/isomiR network in multiple primary melanoma pathogenesis

Author

Giorgio Durante, Cosimo Misciali, Martina Lambertini, Cristian Bassi, Massimo Negrini, Elisa Porcellini, Eric Londin, Mattia Riefolo, Isidore Rigoutsos, Roberta Roncarati, Phillipe Loher, Emi Dika, Annalisa Patrizi, Manuela Ferracin, Elisabetta Broseghini, Dika E., Broseghini E., Porcellini E., Lambertini M., Riefolo M., Durante G., Loher P., Roncarati R., Bassi C., Misciali C., Negrini M., Rigoutsos I., Londin E., Patrizi A., and Ferracin M.

Subjects
Gene isoform, Adult, Cancer Research, Skin Neoplasms, Immunology, multiple melanoma, Biology, medicine.disease_cause, Article, NO, Pathogenesis, Cellular and Molecular Neuroscience, IsomiR, Melanoma, MicroRNAs, Skin Neoplasms, microRNA, isomiR, medicine, melanoma, Humans, Gene, familial melanoma, Aged, Aged, 80 and over, QH573-671, Melanoma, Small RNAs, Cell Biology, Middle Aged, medicine.disease, MicroRNAs, Cancer research, Skin cancer, Carcinogenesis, Cytology
Abstract

Malignant cutaneous melanoma (CM) is a potentially lethal form of skin cancer whose worldwide incidence has been constantly increasing over the past decades. During their lifetime, about 8% of CM patients will develop multiple primary melanomas (MPMs), usually at a young age and within 3 years from the first tumor/diagnosis. With the aim of improving our knowledge on MPM biology and pathogenesis, we explored the miRNome of 24 single and multiple primary melanomas, including multiple tumors from the same patient, using a small RNA-sequencing approach. From a supervised analysis, 22 miRNAs were differentially expressed in MPM compared to single CM, including key miRNAs involved in epithelial–mesenchymal transition. The first and second melanoma from the same patient presented a different miRNA profile. Ten miRNAs, including miR-25-3p, 149-5p, 92b-3p, 211-5p, 125a-5p, 125b-5p, 205-5p, 200b-3p, 21-5p, and 146a-5p, were further validated in 47 single and multiple melanoma samples. Pathway enrichment analysis of miRNA target genes revealed a more differentiated and less invasive status of MPMs compared to CMs. Bioinformatic analyses at the miRNA isoform (isomiR) level detected a panel of highly expressed isomiRs belonging to miRNA families implicated in human tumorigenesis, including miR-200, miR-30, and miR-10 family. Moreover, we identified hsa-miR-125a-5p|0|−2 isoform as tenfold over-represented in melanoma than the canonical form and differentially expressed in MPMs arising in the same patient. Target prediction analysis revealed that the miRNA shortening could change the pattern of target gene regulation, specifically in genes implicated in cell adhesion and neuronal differentiation. Overall, we provided a putative and comprehensive characterization of the miRNA/isomiR regulatory network of MPMs, highlighting mechanisms of tumor development and molecular features differentiating this subtype from single melanomas.

Published
2021

49. Interleukin-6 gene polymorphism is an age-dependent risk factor for myocardial infarction in men

Author

Emanuela Tumini, Cecilia Tampieri, Martina Chiappelli, Elisa Porcellini, Samuele Nanni, Enrico Hoffmann, Marco Caruso, Angelo Branzi, Claudio Marcello Caldarera, Calogero Caruso, Federico Licastro, Domenico Lio, CHIAPPELLI M, TAMPIERI C, TUMINI E, PORCELLINI E, CALDARERA CM, NANNI S, BRANZI A, LIO D, CARUSO M, HOFFMANN E, CARUSO C, LICASTRO F, Chiappelli M, Tampieri C, Tumini E, Porcellini E, Caldarera CM, Nanni S, Branzi A, Lio D, Caruso M, Hoffmann E, Caruso C, and Licastro F.

Subjects
Male, medicine.medical_specialty, Genotype, medicine.medical_treatment, Immunology, Myocardial Infarction, Gastroenterology, Polymorphism, Single Nucleotide, Polymorphism (computer science), Risk Factors, Internal medicine, Genetics, medicine, Humans, Genetic Predisposition to Disease, Myocardial infarction, Risk factor, Allele, Promoter Regions, Genetic, Molecular Biology, Gene, Genetics (clinical), Alleles, Aged, business.industry, Interleukin-6, Age Factors, Promoter, General Medicine, Middle Aged, medicine.disease, C reactive protein, DNA, interleukin 6, Cytokine, C-Reactive Protein, Case-Control Studies, business
Abstract

Summary Several studies show that inflammatory components may contribute to atherosclerosis and increase the risk for myocardial infarction (MI). Interleukin-6 (IL-6) is a key pro-inflammatory and immune-modulatory cytokine of relevance for cardiovascular diseases. In this case-control study, 200 patients with MI and 257 healthy controls were genotyped for the polymorphism present in −174 promoter region of the IL-6 gene. Plasma concentrations of IL-6 and C-reactive protein (CRP) in a group of patients and controls were measured. The −174 C allele was associated with an increased risk of developing MI (OR = 2.886, c.i. = 1.801–4.624, P = 0.0001) in older patients, while no association was found in younger ones. The IL-6 plasma levels were higher in patients with MI carrying the CC genotype than in GG patients (CC carriers, IL-6 = 2.97 pg mL−1 vs. GG carriers = 1.81 pg mL−1, P = 0.016). A positive correlation of IL-6 levels with those of CRP in serum from patients with MI was also found. Data from this study suggest that the C allele of the promoter polymorphism in the IL-6 gene is a risk factor for MI in the elderly, and the production of the IL-6 is differentially affected by different genotypes of the IL-6 −174 promoter polymorphism.

Published
2005

50. INNATE IMMUNITY AND INFLAMMATION IN AGEING: A KEY FOR UNDERSTANDING AGE-RELATED DISEASES

Author

Calogero Caruso, Domenico Lio, Federico Licastro, Giuseppina Candore, Claudio Franceschi, Giuseppina Colonna-Romano, Elisa Porcellini, LICASTRO F, CANDORE G, LIO D, PORCELLINI E, COLONNA ROMANO G, FRANCESCHI C, CARUSO C, Licastro F., Candore G., Lio D., Porcellini E., Colonna-Romano G., Franceschi C., and Caruso C.

Subjects
lcsh:Immunologic diseases. Allergy, Aging, media_common.quotation_subject, Longevity, Immunology, Inflammation, Review, Disease, lcsh:Geriatrics, Systemic inflammation, Immune system, Immunity, medicine, Permissive, Cytokine, media_common, Innate immune system, business.industry, Innate Immunity, lcsh:RC952-954.6, medicine.symptom, lcsh:RC581-607, business, Age-related diseases
Abstract

The process of maintaining life for the individual is a constant struggle to preserve his/her integrity. This can come at a price when immunity is involved, namely systemic inflammation. Inflammation is not per se a negative phenomenon: it is the response of the immune system to the invasion of viruses or bacteria and other pathogens. During evolution the human organism was set to live 40 or 50 years; today, however, the immune system must remain active for much a longer time. This very long activity leads to a chronic inflammation that slowly but inexorably damages one or several organs: this is a typical phenomenon linked to ageing and it is considered the major risk factor for age-related chronic diseases. Alzheimer's disease, atherosclerosis, diabetes and even sarcopenia and cancer, just to mention a few – have an important inflammatory component, though disease progression seems also dependent on the genetic background of individuals. Emerging evidence suggests that pro-inflammatory genotypes are related to unsuccessful ageing, and, reciprocally, controlling inflammatory status may allow a better chance of successful ageing. In other words, age-related diseases are "the price we pay" for a life-long active immune system: this system has also the potential to harm us later, as its fine tuning becomes compromised. Our immune system has evolved to control pathogens, so pro-inflammatory responses are likely to be evolutionarily programmed to resist fatal infections with pathogens aggressively. Thus, inflammatory genotypes are an important and necessary part of the normal host responses to pathogens in early life, but the overproduction of inflammatory molecules might also cause immune-related inflammatory diseases and eventually death later. Therefore, low responder genotypes involved in regulation of innate defence mechanisms, might better control inflammatory responses and age-related disease development, resulting in an increased chance of long life survival in a "permissive" environment with reduced pathogen load, medical care and increased quality of life.

Published
2005

Catalog

Books, media, physical & digital resources
See catalog results