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

被引：486

作者：

Genin, E. ^{[2
,3
]}

Hannequin, D. ^{[4
]}

Wallon, D. ^{[4
]}

Sleegers, K. ^{[5
,6
,7
]}

Hiltunen, M. ^{[8
,9
]}

Combarros, O. ^{[10
,11
]}

Bullido, M. J. ^{[12
,13
]}

Engelborghs, S. ^{[6
,7
,14
,15
]}

De Deyn, P. ^{[6
,7
,14
,15
]}

Berr, C. ^{[16
]}

Pasquier, F. ^{[17
]}

Dubois, B. ^{[18
]}

Tognoni, G. ^{[19
]}

Fievet, N. ^{[20
,21
]}

Brouwers, N. ^{[5
,6
,7
]}

Bettens, K. ^{[5
,6
,7
]}

Arosio, B. ^{[22
]}

Coto, E. ^{[23
]}

Del Zompo, M. ^{[24
]}

Mateo, I. ^{[10
,11
]}

Epelbaum, J. ^{[25
]}

Frank-Garcia, A. ^{[26
]}

Helisalmi, S. ^{[8
,9
]}

Porcellini, E. ^{[27
]}

Pilotto, A. ^{[28
,29
]}

Forti, P. ^{[30
]}

Ferri, R. ^{[31
]}

Scarpini, E. ^{[32
]}

Siciliano, G. ^{[19
]}

Solfrizzi, V. ^{[33
]}

Sorbi, S. ^{[34
]}

Spalletta, G. ^{[35
]}

Valdivieso, F. ^{[12
,13
]}

Vepsalainen, S. ^{[8
,9
]}

Alvarez, V. ^{[23
]}

Bosco, P. ^{[31
]}

Mancuso, M. ^{[19
]}

Panza, F. ^{[33
]}

Nacmias, B. ^{[34
]}

Bossu, P. ^{[35
]}

Hanon, O. ^{[36
]}

Piccardi, P. ^{[24
]}

Annoni, G. ^{[37
]}

Seripa, D. ^{[28
,29
]}

Galimberti, D. ^{[32
]}

Licastro, F. ^{[27
]}

Soininen, H. ^{[8
,9
]}

Dartigues, J-F ^{[38
]}

Kamboh, M. I. ^{[39
,40
]}

Van Broeckhoven, C. ^{[5
,6
,7
]}

机构：

[1] Ctr Hosp Rouvray, Fac Med, INSERM U614, Dept Res, F-76300 Sotteville Les Rouen, France

[2] Inserm UMRS 946, Paris, France

[3] Univ Paris Diderot, Inst Univ Hematol, Paris, France

[4] Fac Med, INSERM U614, Rouen, France

[5] VIB, Dept Mol Genet, Neurodegenerat Brain Dis Grp, Antwerp, Belgium

[6] Inst Born Bunge, Antwerp, Belgium

[7] Univ Antwerp, B-2020 Antwerp, Belgium

[8] Univ Eastern Finland, Dept Neurol, Kuopio, Finland

[9] Kuopio Univ Hosp, SF-70210 Kuopio, Finland

[10] Univ Cantabria, Marques de Valdecilla Univ Hosp, Neurol Serv, E-39005 Santander, Spain

[11] Univ Cantabria, Marques de Valdecilla Univ Hosp, CIBERNED, E-39005 Santander, Spain

[12] Univ Autonoma Madrid, Ctr Biol Mol Severo Ochoa UAM CSIC, Madrid, Spain

[13] Univ Autonoma Madrid, CIBERNED, Madrid, Spain

[14] ZNA Middelheim, Memory Clin, Antwerp, Belgium

[15] ZNA Middelheim, Dept Neurol, Antwerp, Belgium

[16] Univ Montpellier I, INSERM U1061, Montpellier, France

[17] CHRU Lille, Dept Nemol, Lille, France

[18] Hop La Pitie Salpetriere, Paris, France

[19] Univ Pisa, Neurol Clin, Dept Neurosci, Pisa, Italy

[20] INSERM U744, Lille, France

[21] Inst Pasteur, Lille, France

[22] Univ Milan, Osped Maggiore Policlin Mangiagalli & Regina Elen, Fdn IRCCS, Dept Internal Med, Milan, Italy

[23] Hosp Univ Cent Asturias, Mol Genet Unit, Oviedo, Spain

[24] Univ Cagliari, Dept Neurosci, Clin Pharmacol Sect, Cagliari, Italy

[25] Univ Paris 05, Fac Med, INSERM, UMR 894, Paris, France

[26] Hosp Univ La Paz UAM, Serv Neurol, Madrid, Spain

[27] Univ Bologna, Sch Med, Dept Expt Pathol, Bologna, Italy

[28] IRCCS Casa Sollievo Sofferenza, Geriatr Unit, San Giovanni Rotondo, Italy

[29] IRCCS Casa Sollievo Sofferenza, Dept Med Sci, Gerontol Geriatr Res Lab, San Giovanni Rotondo, Italy

[30] Univ Hosp S Orsola Malpighi, Dept Internal Med Cardiol & Hepatol, Bologna, Italy

[31] IRCCS Oasi Maria SS, Turin, Italy

[32] Univ Milan, IRCCS Osped Maggiore Policlin, Fdn Ca Granda, Dino Ferrari Ctr,Dept Neurol Sci, Milan, Italy

[33] Univ Bari, Memory Unit, Ctr Aging Brain, Dept Geriatr, Bari, Italy

[34] Univ Florence, Dept Neurol, Florence, Italy

[35] IRCCS Santa Lucia Fdn, Dept Clin & Behav Neurol, Rome, Italy

[36] Univ Paris 05, Broca Hosp, Paris, France

[37] Univ Milano Bicocca, Dept Clin Med & Prevent, Monza, Italy

[38] Victor Segalen Univ, INSERM U897, Bordeaux, France

[39] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA

[40] Univ Pittsburgh, Alzheimers Dis Res Ctr, Pittsburgh, PA USA

来源：

MOLECULAR PSYCHIATRY | 2011年 / 16卷 / 09期

关键词：

APOE; Alzheimer; genetics; lifetime risks; epidemiology; APOLIPOPROTEIN-E GENOTYPE; LIFETIME RISK; ASSOCIATION; DEMENTIA; LONGEVITY; LEVEL; BRCA1; CR-1; CLU; SEX;

D O I：

10.1038/mp.2011.52

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Apolipoprotein E (APOE) dependent lifetime risks (LTRs) for Alzheimer Disease (AD) are currently not accurately known and odds ratios alone are insufficient to assess these risks. We calculated AD LTR in 7351 cases and 10 132 controls from Caucasian ancestry using Rochester (USA) incidence data. At the age of 85 the LTR of AD without reference to APOE genotype was 11% in males and 14% in females. At the same age, this risk ranged from 51% for APOE44 male carriers to 60% for APOE44 female carriers, and from 23% for APOE34 male carriers to 30% for APOE34 female carriers, consistent with semi-dominant inheritance of a moderately penetrant gene. Using PAQUID (France) incidence data, estimates were globally similar except that at age 85 the LTRs reached 68 and 35% for APOE 44 and APOE 34 female carriers, respectively. These risks are more similar to those of major genes in Mendelian diseases, such as BRCA1 in breast cancer, than those of low-risk common alleles identified by recent GWAS in complex diseases. In addition, stratification of our data by age groups clearly demonstrates that APOE4 is a risk factor not only for late-onset but for early-onset AD as well. Together, these results urge a reappraisal of the impact of APOE in Alzheimer disease. Molecular Psychiatry (2011) 16, 903-907; doi: 10.1038/mp.2011.52; published online 10 May 2011

引用

页码：903 / 907

页数：5

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