Genetic variations in tau-tubulin kinase-1 are linked to Alzheimer's disease in a Spanish case-control cohort

被引：22

作者：

Luis Vazquez-Higuera, Jose ^{[1
,2
]}

Martinez-Garcia, Ana ^{[3
,4
]}

Sanchez-Juan, Pascual ^{[1
,2
]}

Rodriguez-Rodriguez, Eloy ^{[1
,2
]}

Mateo, Ignacio ^{[1
,2
]}

Pozueta, Ana ^{[1
,2
]}

Frank, Ana ^{[5
,6
]}

Valdivieso, Fernando ^{[3
,4
]}

Berciano, Jose ^{[1
,2
]}

Bullido, Maria J. ^{[3
,4
]}

Combarros, Onofre ^{[1
,2
]}

机构：

[1] Univ Cantabria, Marques de Valdecilla Univ Hosp, Neurol Serv, Santander 39008, Spain

[2] Univ Cantabria, Marques de Valdecilla Univ Hosp, CIBERNED, Santander 39008, Spain

[3] UAM, CSIC, Ctr Biol Mol Severo Ochoa, Dept Mol Biol, Madrid, Spain

[4] UAM, CSIC, Ctr Biol Mol Severo Ochoa, CIBERNED, Madrid, Spain

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

[6] UAM, Hosp Univ La Paz, CIBERNED, Madrid, Spain

来源：

NEUROBIOLOGY OF AGING | 2011年 / 32卷 / 03期

关键词：

Alzheimer's disease; Tau-tubulin kinase-1; Tau phosphorylation; Genetic polymorphism; GLYCOGEN-SYNTHASE KINASE-3-BETA; GENOME-WIDE ASSOCIATION; IDENTIFIES VARIANTS; PROTEIN-TAU; PHOSPHORYLATION; DEGENERATION; INTERACT; RISK; CDC2; CLU;

D O I：

10.1016/j.neurobiolaging.2009.12.021

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

Neurofibrillary tangles, one of the characteristic neuropathological lesions found in Alzheimer's disease (AD) brains, are composed of abnormally hyperphosphorylated tau protein. Tau-tubulin kinase-1 (TTBK1) is a brain-specific protein kinase involved in tau phosphorylation at AD-related sites. We examined genetic variations of TTBK1 by genotyping nine haplotype tagging SNPs (htSNPs) (rs2104142, rs2651206, rs10807287, rs7764257, rs3800294, rs1995300, rs2756173, rs6936397, and rs6458330) in a group of 645 Spanish late-onset AD patients and 738 healthy controls. Using a recessive genetic model, minor allele homozygotes for rs2651206 in intron 1 (OR=0.50, p=0.0003), rs10807287 in intron 5 (OR=0.49, p=0.0002), and rs7764257 in intron 9 (OR=0.57, p=0.023), which are in strong linkage disequilibrium, had a lower risk of developing AD than subjects homozygotes and heterozygotes for the major allele. TTBK1 is a promising new candidate tau phosphorylation-related gene for AD risk. (C) 2010 Elsevier Inc. All rights reserved.

引用

页码：550.e5 / 550.e9

页数：5

共 17 条

[1] Cyclin-dependent kinase 5 is associated with risk for Alzheimer's diseasein a Dutch population-based study [J].

Arias-Vasquez, Alejandro ;

Aulchenko, Yurii S. ;

Isaacs, Aaron ;

van Oosterhout, Andy ;

Sleegers, Kristel ;

Hofman, Albert ;

van Broeckhoven, Christine ;

Oostra, Ben A. ;

Breteler, Monique ;

van Duijn, Cornelia M. .

JOURNAL OF NEUROLOGY, 2008, 255 (05) :655-662

[2] The CDC2 I-G-T haplotype associated with the APOE ε4 allele increases the risk of sporadic Alzheimer's disease in Sicily [J].

Bosco, Paolo ;

Caraci, Filippo ;

Copani, Agata ;

Spada, Rosario S. ;

Sortino, Maria Angela ;

Salluzzo, Roberto ;

Salemi, Michele ;

Nicoletti, Ferdinando ;

Ferri, Raffaele .

NEUROSCIENCE LETTERS, 2007, 419 (03) :195-198

[3] Glycogen Synthase Kinase-3β and Tau Genes Interact in Parkinson's and Alzheimer's Diseases [J].

Garcia-Gorostiaga, Ines ;

Sanchez-Juan, Pascual ;

Mateo, Ignacio ;

Rodriguez-Rodriguez, Eloy ;

Sanchez-Quintana, Coro ;

Curiel del Olmo, Soraya ;

Luis Vazquez-Higuera, Jose ;

Berciano, Jose ;

Combarros, Onofre ;

Infante, Jon .

ANNALS OF NEUROLOGY, 2009, 65 (06) :759-761

[4]

Harold D, 2009, NAT GENET, V41, P1088, DOI 10.1038/ng.440

[5] Mutations in TTBK2, encoding a kinase implicated in tau phosphorylation, segregate with spinocerebellar ataxia type 11 [J].

Houlden, Henry ;

Johnson, Janel ;

Gardner-Thorpe, Christopher ;

Lashley, Tammaryn ;

Hernandez, Dena ;

Worth, Paul ;

Singleton, Andrew B. ;

Hilton, David A. ;

Holton, Janice ;

Revesz, Tamas ;

Davis, Mary B. ;

Giunti, Paolo ;

Wood, Nicholas W. .

NATURE GENETICS, 2007, 39 (12) :1434-1436

[6] Alzheimer neurofibrillary degeneration: significance, etiopathogenesis, therapeutics and prevention [J].

Iqbal, K. ;

Grundke-Iqbal, I. .

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2008, 12 (01) :38-55

[7] Mechanisms of tau-induced neurodegeneration [J].

Iqbal, Khalid ;

Liu, Fei ;

Gong, Cheng-Xin ;

Alonso, Alejandra del C. ;

Grundke-Iqbal, Inge .

ACTA NEUROPATHOLOGICA, 2009, 118 (01) :53-69

[8] Genetic association of CDC2 with cerebrospinal fluid tau in Alzheimer's disease [J].

Johansson, A ;

Zetterberg, H ;

Hampel, H ;

Buerger, K ;

Prince, JA ;

Minthon, L ;

Wahlund, LO ;

Blennow, K .

DEMENTIA AND GERIATRIC COGNITIVE DISORDERS, 2005, 20 (06) :367-374

[9] Glycogen Synthase Kinase-3β and Tau Genes Interact in Alzheimer's Disease [J].

Kwok, John B. J. ;

Loy, Clement T. ;

Hamilton, Gillian ;

Lau, Edmond ;

Hallupp, Marianne ;

Williams, Julie ;

Owen, Michael J. ;

Broe, G. Anthony ;

Tang, Nelson ;

Lam, Linda ;

Powell, John F. ;

Lovestone, Simon ;

Schofield, Peter R. .

ANNALS OF NEUROLOGY, 2008, 64 (04) :446-454

[10] Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease [J].

Lambert, Jean-Charles ;

Heath, Simon ;

Even, Gael ;

Campion, Dominique ;

Sleegers, Kristel ;

Hiltunen, Mikko ;

Combarros, Onofre ;

Zelenika, Diana ;

Bullido, Maria J. ;

Tavernier, Beatrice ;

Letenneur, Luc ;

Bettens, Karolien ;

Berr, Claudine ;

Pasquier, Florence ;

Fievet, Nathalie ;

Barberger-Gateau, Pascale ;

Engelborghs, Sebastiaan ;

De Deyn, Peter ;

Mateo, Ignacio ;

Franck, Ana ;

Helisalmi, Seppo ;

Porcellini, Elisa ;

Hanon, Olivier ;

de Pancorbo, Marian M. ;

Lendon, Corinne ;

Dufouil, Carole ;

Jaillard, Celine ;

Leveillard, Thierry ;

Alvarez, Victoria ;

Bosco, Paolo ;

Mancuso, Michelangelo ;

Panza, Francesco ;

Nacmias, Benedetta ;

Bossu, Paola ;

Piccardi, Paola ;

Annoni, Giorgio ;

Seripa, Davide ;

Galimberti, Daniela ;

Hannequin, Didier ;

Licastro, Federico ;

Soininen, Hilkka ;

Ritchie, Karen ;

Blanche, Helene ;

Dartigues, Jean-Francois ;

Tzourio, Christophe ;

Gut, Ivo ;

Van Broeckhoven, Christine ;

Alperovitch, Annick ;

Lathrop, Mark ;

Amouyel, Philippe .

NATURE GENETICS, 2009, 41 (10) :1094-U68

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