SUCLG2 identified as both a determinator of CSF Aβ1-42 levels and an attenuator of cognitive decline in Alzheimer's disease

被引：39

作者：

Ramirez, Alfredo ^{[1
,2
]}

van der Flier, Wiesje M. ^{[6
,7
,8
]}

Herold, Christine ^{[9
]}

Ramonet, David ^{[3
]}

Heilmann, Stefanie ^{[2
,4
]}

Lewczuk, Piotr ^{[10
,11
]}

Popp, Julius ^{[1
]}

Lacour, Andre ^{[9
]}

Drichel, Dmitriy ^{[9
]}

Louwersheimer, Eva ^{[6
,7
,8
]}

Kummer, Markus P. ^{[3
,9
]}

Cruchaga, Carlos ^{[12
,13
]}

Hoffmann, Per ^{[2
,4
,15
,16
]}

Teunissen, Charlotte ^{[6
,7
,8
]}

Holstege, Henne ^{[6
,7
,8
]}

Kornhuber, Johannes ^{[10
,11
]}

Peters, Oliver ^{[17
]}

Naj, Adam C. ^{[18
]}

Chouraki, Vincent ^{[19
,20
]}

Bellenguez, Celine ^{[21
,22
,23
]}

Gerrish, Amy ^{[24
]}

Heun, Reiner ^{[1
]}

Froelich, Lutz ^{[25
]}

Huell, Michael ^{[26
,27
]}

Buscemi, Lara ^{[28
]}

Herms, Stefan ^{[2
,4
,15
,16
]}

Koelsch, Heike ^{[1
]}

Scheltens, Philip ^{[6
,7
,8
]}

Breteler, Monique M. ^{[9
]}

Ruether, Eckart ^{[29
]}

Wiltfang, Jens ^{[29
]}

Goate, Alison ^{[12
,14
]}

Jessen, Frank ^{[1
,9
]}

Maier, Wolfgang ^{[1
,9
]}

Heneka, Michael T. ^{[3
,9
]}

Becker, Tim ^{[5
,9
]}

Noethen, Markus M. ^{[2
,4
]}

机构：

[1] Univ Bonn, Dept Psychiat & Psychotherapy, D-53127 Bonn, Germany

[2] Univ Bonn, Inst Human Genet, D-53127 Bonn, Germany

[3] Univ Bonn, Dept Neurol, Clin Neurosci Unit, D-53127 Bonn, Germany

[4] Univ Bonn, Dept Genom, Life & Brain Ctr, D-53127 Bonn, Germany

[5] Univ Bonn, Inst Med Biometry Informat & Epidemiol, D-53127 Bonn, Germany

[6] Vrije Univ Amsterdam, Med Ctr, Dept Neurol, NL-1081 HZ Amsterdam, Netherlands

[7] Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, Neurosci Campus Amsterdam, NL-1081 HZ Amsterdam, Netherlands

[8] Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, NL-1007 MB Amsterdam, Netherlands

[9] German Ctr Neurodegenerat Dis DZNE, D-53175 Bonn, Germany

[10] Univ Klinikum Erlangen, Dept Psychiat & Psychotherapy, D-91054 Erlangen, Germany

[11] Univ Erlangen Nurnberg, D-91054 Erlangen, Germany

[12] Washington Univ, Dept Psychiat, St Louis, MO 63110 USA

[13] Washington Univ, Sch Med, Hope Ctr Neurol Disorders, St Louis, MO 63110 USA

[14] Washington Univ, Dept Genet, St Louis, MO 63110 USA

[15] Univ Basel, Univ Hosp, Div Med Genet, CH-4058 Basel, Switzerland

[16] Univ Basel, Dept Biomed, CH-4058 Basel, Switzerland

[17] Charite, Dept Psychiat, D-14050 Berlin, Germany

[18] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA

[19] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA

[20] Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA

[21] INSERM, U744, F-59000 Lille, France

[22] Univ Lille 2, F-59000 Lille, France

[23] Inst Pasteur, F-59000 Lille, France

[24] Cardiff Univ, Inst Psychol Med & Clin Neurosci, MRC Ctr Neuropsychiat Genet & Genom, Cardiff CF10 3AX, S Glam, Wales

[25] Heidelberg Univ, Dept Geriatr Psychiat, Cent Inst Mental Hlth, Med Fac Mannheim, D-68159 Mannheim, Germany

[26] Univ Freiburg, Ctr Geriatr Med, D-79106 Freiburg, Germany

[27] Univ Freiburg, Sect Gerontopsychiat & Neuropsychol, Sch Med, D-79106 Freiburg, Germany

[28] UNIL, Dept Fundamental Neurosci, CH-1005 Lausanne, Switzerland

[29] Univ Gottingen, Dept Psychiat & Psychotherapy, D-37075 Gottingen, Germany

来源：

HUMAN MOLECULAR GENETICS | 2014年 / 23卷 / 24期

基金：

加拿大健康研究院; 美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; AMYLOID CLEARANCE; COMMON VARIANTS; A-BETA; DIAGNOSIS; METAANALYSIS; DEMENTIA; MICROGLIA; CD33; RISK;

D O I：

10.1093/hmg/ddu372

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：

Cerebrospinal fluid amyloid-beta 1-42 (A beta(1-42)) and phosphorylated Tau at position 181 (pTau(181)) are biomarkers of Alzheimer's disease (AD). We performed an analysis and meta-analysis of genome-wide association study data on A beta(1-42) and pTau(181) in AD dementia patients followed by independent replication. An association was found between A beta(1-42) level and a single-nucleotide polymorphism in SUCLG2 (rs62256378) (P = 2.5 x 10(-12)). An interaction between APOE genotype and rs62256378 was detected (P = 9.5 x 10(-5)), with the strongest effect being observed in APOE-epsilon 4 noncarriers. Clinically, rs62256378 was associated with rate of cognitive decline in AD dementia patients (P = 3.1 x 10(-3)). Functional microglia experiments showed that SUCLG2 was involved in clearance of A beta(1-42).

引用

页码：6644 / 6658

页数：15

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