Increased frequency of a new polymorphism in the cycle 2 (cdc2) gene in patients with Alzheimer's disease frontotemporal dementia

被引:26
作者
Johansson, A
Hampel, H
Faltraco, F
Buerger, K
Minthon, L
Bogdanovic, N
Sjögren, M
Zetterberg, H
Forsell, L
Lilius, L
Wahlund, LO
Rymo, L
Prince, JA
Blennow, K
机构
[1] Gothenburg Univ, Sahlgrenska Acad, Dept Clin Neurosci, Unit Neurochem, Gothenburg, Sweden
[2] Univ Munich, Dept Psychiat, D-8000 Munich, Germany
[3] Malmo Univ Hosp, Dept Clin Neurosci, Neuropsychiat Clin, Malmo, Sweden
[4] Huddinge Univ Hosp, Karolinska Inst, Geriatr Med Sect, Dept Clin Neurosci & Family Med, Stockholm, Sweden
[5] Gothenburg Univ, Sahlgrenska Acad, Dept Clin Chem & Transfus Med, Gothenburg, Sweden
[6] Karolinska Inst, Ctr Genom & Bioinformat, Stockholm, Sweden
[7] MRC, Stockholm, Sweden
关键词
Alzheimer's disease; frontotemporal dementia; cdc2; apolipoprotein E; senile plaques;
D O I
10.1016/S0304-3940(03)00051-X
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Recent studies show linkage between Alzheimer's disease (AD) and two loci on chromosome 10. The cell division cycle 2 (cdc2) gene is located close to one of the chromosome 10 markers, and is a candidate gene for AD since it is involved in the pathogenesis of AD. We sequenced coding exons and flanking intronic sequences and the promoter region on the cdc2 gene and found three new single nucleotide polymorphisms (SNPs). We analyzed 272 Caucasian AD cases, 160 controls and 70 cases with frontotemporal dementia (FTD) for these SNPs. Homozygosity for one of the SNPs (Ex6 + 7I/D) was more frequent in both AD and FTD cases than in controls. In the combined tauopathy (AD and FTD) group the odds ratio (OR) was 1.77 (95% CI 1.19-2.63) for the Ex6 + 7II genotype. Our findings suggest that the Ex6 + 7I allele is associated with tauopathies, both AD and FrD. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:69 / 73
页数:5
相关论文
共 17 条
[1]   Evidence for genetic linkage of Alzheimer's disease to chromosome 10q [J].
Bertram, L ;
Blacker, D ;
Mullin, K ;
Keeney, D ;
Jones, J ;
Basu, S ;
Yhu, S ;
McInnis, MG ;
Go, RCP ;
Vekrellis, K ;
Selkoe, DJ ;
Saunders, AJ ;
Tanzi, RE .
SCIENCE, 2000, 290 (5500) :2302-+
[2]   Genetic testing for Alzheimer's disease: how close is reality? [J].
Blennow, K ;
Skoog, I .
CURRENT OPINION IN PSYCHIATRY, 1999, 12 (04) :487-493
[3]   No association between the α2-macroglobulin (A2M) deletion and Alzheimer's disease, and no change in A2M mRNA, protein, or protein expression [J].
Blennow, K ;
Ricksten, A ;
Prince, JA ;
Brookes, AJ ;
Emahazion, T ;
Wasslavik, C ;
Bogdanovic, N ;
Andreasen, N ;
Båtsman, S ;
Marcusson, J ;
Nägga, K ;
Wallin, A ;
Regland, B ;
Olofsson, H ;
Hesse, C ;
Davidson, P ;
Minthon, L ;
Jansson, A ;
Palmqvist, L ;
Rymo, L .
JOURNAL OF NEURAL TRANSMISSION, 2000, 107 (8-9) :1065-1079
[4]   Linkage of plasma Aβ42 to a quantitative locus on chromosome 10 in late-onset Alzheimer's disease pedigrees [J].
Ertekin-Taner, N ;
Graff-Radford, N ;
Younkin, LH ;
Eckman, C ;
Baker, M ;
Adamson, J ;
Ronald, J ;
Blangero, J ;
Hutton, M ;
Younkin, SG .
SCIENCE, 2000, 290 (5500) :2303-+
[5]   Timing of events in mitosis [J].
Georgi, AB ;
Stukenberg, PT ;
Kirschner, MW .
CURRENT BIOLOGY, 2002, 12 (02) :105-114
[6]   Genetic classification of primary neurodegenerative disease [J].
Hardy, J ;
Gwinn-Hardy, K .
SCIENCE, 1998, 282 (5391) :1075-1079
[7]   Neurodegenerative tauopathies [J].
Lee, VMY ;
Goedert, M ;
Trojanowski, JQ .
ANNUAL REVIEW OF NEUROSCIENCE, 2001, 24 :1121-1159
[8]  
MCKHANN G, 1984, NEUROLOGY, V34, P939, DOI 10.1212/WNL.34.7.939
[9]  
McShea A, 1997, AM J PATHOL, V150, P1933
[10]   Phosphorylation of amyloid-β at the serine 26 residue by human cdc2 kinase [J].
Milton, NGN .
NEUROREPORT, 2001, 12 (17) :3839-3844