Genetic risk score predicting accelerated progression from mild cognitive impairment to Alzheimer’s disease

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• 作者：E. Rodríguez-Rodríguez (1)
  P. Sánchez-Juan (1)
  J. L. Vázquez-Higuera (1)
  I. Mateo (1)
  A. Pozueta (1)
  J. Berciano (1)
  S. Cervantes (2)
  D. Alcolea (3)
  P. Martínez-Lage (4)
  J. Clarimón (3)
  A. Lleó (3)
  P. Pastor (2) (5)
  O. Combarros (1)
  
• 关键词：Mild cognitive impairment ; Alzheimer’s disease ; Conversion ; Genetics ; Risk ; Genetic risk score
• 刊名：Journal of Neural Transmission
• 出版年：2013
• 出版时间：May 2013
• 年：2013
• 卷：120
• 期：5
• 页码：807-812
• 全文大小：210KB
• 参考文献：1. Barabash A, Marcos A, Ancín I, Vázquez-Alvarez B, de Ugarte C, Gil P, Fernández C, Encinas M, López-Ibor JJ, Cabranes JA (2009) APOE, ACT and CHRNA7 genes in the conversion from amnestic mild cognitive impairment to Alzheimer’s disease. Neurobiol Aging 30:1254-264 CrossRef
  2. Bertram L, McQueen MB, Mullin K, Blacker D, Tanzi RE (2007) Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database. Nat Genet 39:17-3 CrossRef
  3. Busse A, Matthias C, Angermeyer C, Riedel-Heller SG (2006) Progression of mild cognitive impairment to dementia: a challenge to current thinking. Brit J Psychiatry 189:399-04 CrossRef
  4. Cervantes S, Samaranch L, Vidal-Taboada JM, Lamet I, Bullido MJ, Frank-García A, Coria F, Lleó A, Clarimón J, Lorenzo E, Alonso E, Sánchez-Juan P, Rodríguez-Rodríguez E, Combarros O, Rosich M, Vilella E, Pastor P (2011) Genetic variation in APOE cluster region and Alzheimer’s disease risk. Neurobiol Aging 22: 2107.e7-7
  5. Chiappelli M, Borroni B, Archetti S, Calabrese E, Corsi MM, Franceschi M, Padovani A, Licastro F (2006) VEGF gene and phenotype relation with Alzheimer's disease and mild cognitive impairment. Rejuvenation Res 9:485-93 CrossRef
  6. Cornelis MC, Qi L, Zhang C, Kraft P, Manson J, Cai T, Hunter DJ, Hu FB (2009) Joint effects of common genetic variants on the risk for type 2 diabetes in U.S. men and women of European ancestry. Ann Intern Med 150:541-50 CrossRef
  7. Davatzikos C, Bhatt P, Shaw LM, Batmanghelich KN, Trojanowski JQ (2011) Prediction of MCI to AD conversion, via MRI, CSF biomarkers, and pattern classification. Neurobiol Aging 32: 2322.e19-7
  8. De Jager PL, Chibnik LB, Cui J, Reischl J, Lehr S, Simon KC, Aubin C, Bauer D, Heubach JF, Sandbrink R, Tyblova M, Lelkova P; Steering committee of the BENEFIT study; Steering committee of the BEYOND study; Steering committee of the LTF study; Steering committee of the CCR1 study, Havrdova E, Pohl C, Horakova D, Ascherio A, Hafler DA, Karlson EW (2009) Integration of genetic risk factors into a clinical algorithm for multiple sclerosis susceptibility: a weighted genetic risk score. Lancet Neurol 8:1111-119
  9. Elias-Sonnenschein LS, Viechtbauer W, Ramakers IH, Verhey FR, Visser PJ (2011) Predictive value of APOE-ε4 allele for progression from MCI to AD-type dementia: a meta-analysis. J Neurol Neurosurg Psychiatry 82: 1149-156
  10. Ferris S, Nordberg A, Soininen H, Darreh-Shori T, Lane R (2009) Progression from mild cognitive impairment to Alzheimer’s disease: effects of sex, butyrylcholinesterase genotype, and rivastigmine treatment. Pharmacogenet Genomics 19:635-46 CrossRef
  11. Forlenza OV, Diniz BS, Teixeira AL, Ojopi EB, Talib LL, Mendon?a VA, Izzo G, Gattaz WF (2010) Effect of brain-derived neurotrophic factor Val66Met polymorphism and serum levels on the progression of mild cognitive impairment. World J Biol Psychiatry 11:774-80 CrossRef
  12. Harold D, Abraham R, Hollingworth P, Sims R, Gerrish A, Hamshere ML, Pahwa JS, Moskvina V, Dowzell K, Williams A, Jones N, Thomas C, Stretton A, Morgan AR, Lovestone S, Powell J, Proitsi P, Lupton MK, Brayne C, Rubinsztein DC, Gill M, Lawlor B, Lynch A, Morgan K, Brown KS, Passmore PA, Craig D, McGuinness B, Todd S, Holmes C, Mann D, Smith AD, Love S, Kehoe PG, Hardy J, Mead S, Fox N, Rossor M, Collinge J, Maier W, Jessen F, Schürmann B, van den Bussche H, Heuser I, Kornhuber J, Wiltfang J, Dichgans M, Fr?lich L, Hampel H, Hüll M, Rujescu D, 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, N?then MM, Moebus S, J?ckel KH, Klopp N, Wichmann HE, Carrasquillo MM, Pankratz VS, Younkin SG, Holmans PA, O’Donovan M, Owen MJ, Williams J (2009) Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease. Nat Genet 41:1088-093 CrossRef
  13. 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, K?lsch H, van den Bussche H, Heuser I, Kornhuber J, Wiltfang J, Dichgans M, Fr?lich 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, N?then MM, Moebus S, J?ckel KH, Klopp N, Wichmann HE, Pankratz VS, Sando SB, Aasly JO, Barcikowska M, Wszolek ZK, Dickson DW, Graff-Radford NR, Petersen RC; the 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, Sn?dal J, Bj?rnsson 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 (2011) Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease. Nat Genet 43:429-35
  14. Jack CR Jr, Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW, Petersen RC, Trojanowski JQ (2010) Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. Lancet Neurol 9:119-28 CrossRef
  15. Karlson EW, Chibnik LB, Kraft P, Cui J, Keenan BT, Ding B, Raychaudhuri S, Klareskog L, Alfredsson L, Plenge RM (2010) Cumulative association of twenty-two genetic variants with seropositive rheumatoid arthritits risk. Ann Rheum Dis 69:1077-085 CrossRef
  16. 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 (2009) Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease. Nat Genet 41:1094-099
  17. Landau SM, Harvey D, Madison CM, Reiman EM, Foster NL, Aisen PS, Petersen RC, Shaw LM, Trojanowski JQ, Jack CR Jr, Weiner MW, Jagust WJ; Alzheimer’s Disease Neuroimaging Initiative (2010) Comparing predictors of conversion and decline in mild cognitive impairment. Neurology 75:230-38
  18. Naj AC, Jun G, Beecham GW, Wang LS, Vardarajan BN, Buros J, Gallins PJ, Buxbaum JD, Jarvik GP, Crane PK, Larson EB, Bird TD, Boeve BF, Graff-Radford NR, De Jager PL, Evans D, Schneider JA, Carrasquillo MM, Ertekin-Taner N, Younkin SG, Cruchaga C, Kauwe JS, Nowotny P, Kramer P, Hardy J, Huentelman MJ, Myers AJ, Barmada MM, Demirci FY, Baldwin CT, Green RC, Rogaeva E, St George-Hyslop P, Arnold SE, Barber R, Beach T, Bigio EH, Bowen JD, Boxer A, Burke JR, Cairns NJ, Carlson CS, Carney RM, Carroll SL, Chui HC, Clark DG, Corneveaux J, Cotman CW, Cummings JL, DeCarli C, DeKosky ST, Diaz-Arrastia R, Dick M, Dickson DW, Ellis WG, Faber KM, Fallon KB, Farlow MR, Ferris S, Frosch MP, Galasko DR, Ganguli M, Gearing M, Geschwind DH, Ghetti B, Gilbert JR, Gilman S, Giordani B, Glass JD, Growdon JH, Hamilton RL, Harrell LE, Head E, Honig LS, Hulette CM, Hyman BT, Jicha GA, Jin LW, Johnson N, Karlawish J, Karydas A, Kaye JA, Kim R, Koo EH, Kowall NW, Lah JJ, Levey AI, Lieberman AP, Lopez OL, Mack WJ, Marson DC, Martiniuk F, Mash DC, Masliah E, McCormick WC, McCurry SM, McDavid AN, McKee AC, Mesulam M, Miller BL, Miller CA, Miller JW, Parisi JE, Perl DP, Peskind E, Petersen RC, Poon WW, Quinn JF, Rajbhandary RA, Raskind M, Reisberg B, Ringman JM, Roberson ED, Rosenberg RN, Sano M, Schneider LS, Seeley W, Shelanski ML, Slifer MA, Smith CD, Sonnen JA, Spina S, Stern RA, Tanzi RE, Trojanowski JQ, Troncoso JC, Van Deerlin VM, Vinters HV, Vonsattel JP, Weintraub S, Welsh-Bohmer KA, Williamson J, Woltjer RL, Cantwell LB, Dombroski BA, Beekly D, Lunetta KL, Martin ER, Kamboh MI, Saykin AJ, Reiman EM, Bennett DA, Morris JC, Montine TJ, Goate AM, Blacker D, Tsuang DW, Hakonarson H, Kukull WA, Foroud TM, Haines JL, Mayeux R, Pericak-Vance MA, Farrer LA, Schellenberg GD (2011) Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer’s disease. Nat Genet 43:436-41 CrossRef
  19. Petersen RC, Doody R, Kurz A, Mohs RC, Morris JC, Rabins PV, Ritchie K, Rossor M, Thal L, Winblad B (2001) Current concepts in mild cognitive impairment. Arch Neurol 58:1985-992 CrossRef
  20. Pozueta A, Vázquez-Higuera JL, Sánchez-Juan P, Rodríguez-Rodríguez E, Sánchez-Quintana C, Mateo I, Berciano J, Combarros O (2011) Genetic variation in caspase-1 as predictor of accelerated progression from mild cognitive impairment to Alzheimer’s disease. J Neurol 258:1538-539 CrossRef
  21. Reitz C, Mayeux R (2010) Use of genetic variation as biomarkers for mild cognitive impairment and progression of mild cognitive impairment to dementia. J Alzheimers Dis 19:229-51
  22. Ripatti S, Tikkanen E, Orho-Melander M, Havulinna AS, Silander K, Sharma A, Guiducci C, Perola M, Jula A, Sinisalo J, Lokki ML, Nieminen MS, Melander O, Salomaa V, Peltonen L, Kathiresan S (2010) A multilocus genetic risk score for coronary heart disease: case-control and prospective cohort analyses. Lancet 376:1393-400 CrossRef
  23. Samaranch L, Cervantes S, Barabash A, Alonso A, Cabranes JA, Lamet I, Ancín I, Lorenzo E, Martínez-Lage P, Marcos A, Clarimón J, Alcolea D, Lleó A, Blesa R, Gómez-Isla T, Pastor P (2010) The effect of MAPT H1 and APOE ε4 on transition from mild cognitive impairment to dementia. J Alzheimers Dis 22:1065-071
  24. Seshadri S, Fitzpatrick AL, Ikram MA, DeStefano AL, Gudnason V, Boada M, Bis JC, Smith AV, Carassquillo MM, Lambert JC, Harold D, Schrijvers EM, Ramirez-Lorca R, Debette S, Longstreth WT Jr, Janssens AC, Pankratz VS, Dartigues JF, Hollingworth P, Aspelund T, Hernandez I, Beiser A, Kuller LH, Koudstaal PJ, Dickson DW, Tzourio C, Abraham R, Antunez C, Du Y, Rotter JI, Aulchenko YS, Harris TB, Petersen RC, Berr C, Owen MJ, Lopez-Arrieta J, Varadarajan BN, Becker JT, Rivadeneira F, Nalls MA, Graff-Radford NR, Campion D, Auerbach S, Rice K, Hofman A, Jonsson PV, Schmidt H, Lathrop M, Mosley TH, Au R, Psaty BM, Uitterlinden AG, Farrer LA, Lumley T, Ruiz A, Williams J, Amouyel P, Younkin SG, Wolf PA, Launer LJ, Lopez OL, van Duijn CM, Breteler MM; CHARGE Consortium; GERAD1 Consortium; EADI1 Consortium (2010) Genome-wide analysis of genetic loci associated with Alzheimer disease. JAMA 303:1832-840
  
• 作者单位：E. Rodríguez-Rodríguez (1)
  P. Sánchez-Juan (1)
  J. L. Vázquez-Higuera (1)
  I. Mateo (1)
  A. Pozueta (1)
  J. Berciano (1)
  S. Cervantes (2)
  D. Alcolea (3)
  P. Martínez-Lage (4)
  J. Clarimón (3)
  A. Lleó (3)
  P. Pastor (2) (5)
  O. Combarros (1)
  
  1. Neurology Service, Neurology Department and CIBERNED, “Marqués de Valdecilla-University Hospital (University of Cantabria and IFIMAV), 39008, Santander, Spain
  2. Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
  3. Neurology Department and CIBERNED, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
  4. Fundación CITA-Alzheimer, San Sebastián, Spain
  5. Neurology Department and CIBERNED, Clínica Universidad de Navarra, Pamplona, Spain
  
• ISSN：1435-1463

文摘

Aside from APOE, the genetic factors that influence the progression from mild cognitive impairment (MCI) to Alzheimer’s disease (AD) remain largely unknown. We assessed whether a genetic risk score (GRS), based on eight non-APOE genetic variants previously associated with AD risk in genome-wide association studies, is associated with either risk of conversion or with rapid progression from MCI to AD. Among 288 subjects with MCI, follow-up (mean 26.3?months) identified 118 MCI-converters to AD and 170 MCI-nonconverters. We genotyped ABCA7 rs3764650, BIN1 rs744373, CD2AP rs9296559, CLU rs1113600, CR1 rs1408077, MS4A4E rs670139, MS4A6A rs610932, and PICALM rs3851179. For each subject we calculated a cumulative GRS, defined as the number of risk alleles (range 0-6) with each allele weighted by the AD risk odds ratio. GRS was not associated with risk of conversion from MCI to AD. However, MCI-converters to AD harboring six or more risk alleles (second and third GRS tertiles) progressed twofold more rapidly to AD when compared with those with less than six risk alleles (first GRS tertile). Our GRS is a first step toward development of prediction models for conversion from MCI to AD that incorporate aggregate genetic factors.