共 35 条
Sequence variants of IDE are associated with the extent of β-amyloid deposition in the Alzheimer's disease brain
被引:42
作者:

Blomqvist, MEL
论文数: 0 引用数: 0
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机构: Karolinska Inst, Ctr Genome & Bioinformat, Stockholm, Sweden

Chalmers, K
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机构: Karolinska Inst, Ctr Genome & Bioinformat, Stockholm, Sweden

Andreasen, N
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机构: Karolinska Inst, Ctr Genome & Bioinformat, Stockholm, Sweden

Bogdanovic, N
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机构: Karolinska Inst, Ctr Genome & Bioinformat, Stockholm, Sweden

Wilcock, GK
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机构: Karolinska Inst, Ctr Genome & Bioinformat, Stockholm, Sweden

Cairns, NJ
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机构: Karolinska Inst, Ctr Genome & Bioinformat, Stockholm, Sweden

Feuk, L
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机构: Karolinska Inst, Ctr Genome & Bioinformat, Stockholm, Sweden

Brookes, AJ
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机构: Karolinska Inst, Ctr Genome & Bioinformat, Stockholm, Sweden

Love, S
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h-index: 0
机构: Karolinska Inst, Ctr Genome & Bioinformat, Stockholm, Sweden

Blennow, K
论文数: 0 引用数: 0
h-index: 0
机构: Karolinska Inst, Ctr Genome & Bioinformat, Stockholm, Sweden

Kehoe, PG
论文数: 0 引用数: 0
h-index: 0
机构: Karolinska Inst, Ctr Genome & Bioinformat, Stockholm, Sweden

Prince, JA
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h-index: 0
机构:
Karolinska Inst, Ctr Genome & Bioinformat, Stockholm, Sweden Karolinska Inst, Ctr Genome & Bioinformat, Stockholm, Sweden
机构:
[1] Karolinska Inst, Ctr Genome & Bioinformat, Stockholm, Sweden
[2] Univ Bristol, Dept Clin Sci Care Elderly, Frenchay Hosp, Bristol, Avon, England
[3] Huddinge Univ Hosp, Dept Geriatr Med, Neurotec, Stockholm, Sweden
[4] Huddinge Univ Hosp, Dept Clin Neurosci Occupat Therapy & Elderly Care, Div Geriatr Med B84, S-14186 Huddinge, Sweden
[5] Univ Penn, Sch Med, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA
[6] Hosp Sick Children, Ctr Appl Genome, Toronto, ON M5G 1X8, Canada
[7] Univ Bristol, Frenchay Hosp, Inst Clin Neurosci, Dept Neuropathol, Bristol, Avon, England
[8] Univ Gothenburg, Sahlgrens Univ Hosp, Dept Clin Neurosci & Transfus Med, Gothenburg, Sweden
关键词:
IDE;
linkage disequilibrium;
Alzheimer's disease;
beta-amyloid;
D O I:
10.1016/j.neurobiolaging.2004.07.011
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:
Insulin degrading enzyme, encoded by IDE, plays a primary role in the degradation of amyloid P-protein (A beta), the deposition of which in senile plaques is one of the defining hallmarks of Alzheimer's disease (AD). We recently identified haplotypes in a broad linkage disequilibrium (LD) block encompassing IDE that associate with several AD-related quantitative traits. Here, by examining 32 polymorphic markers extending across IDE and testing quantitative measures of plaque density and cognitive function in three independent Swedish AD samples, we have refined the probable position of pathogenic sequences to a 3' region of IDE, with local maximum effects in the proximity of marker rs 1887922. To replicate these findings, a subset of variants were examined against measures of brain A beta load in an independent English AD sample, whereby maximum effects were again observed for rs1887922. For both Swedish and English autopsy materials, variation at rs1887922 explained approximately 10% of the total variance in the respective histopathology traits. However, across all clinical materials studied to date, this variant site does not appear to associate directly with disease, suggesting that IDE may affect AD severity rather than risk. Results indicate that alleles of IDE contribute to variability in A beta deposition in the AD brain and suggest that this relationship may have relevance for the degree of cognitive dysfunction in AD patients. (c) 2004 Elsevier Inc. All rights reserved.
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页码:795 / 802
页数:8
相关论文
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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-+

Ertekin-Taner, N
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机构: Mayo Clin Jacksonville, Jacksonville, FL 32224 USA

Graff-Radford, N
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机构: Mayo Clin Jacksonville, Jacksonville, FL 32224 USA

Younkin, LH
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机构: Mayo Clin Jacksonville, Jacksonville, FL 32224 USA

Eckman, C
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机构: Mayo Clin Jacksonville, Jacksonville, FL 32224 USA

Baker, M
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机构: Mayo Clin Jacksonville, Jacksonville, FL 32224 USA

Adamson, J
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机构: Mayo Clin Jacksonville, Jacksonville, FL 32224 USA

Ronald, J
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机构: Mayo Clin Jacksonville, Jacksonville, FL 32224 USA

Blangero, J
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机构: Mayo Clin Jacksonville, Jacksonville, FL 32224 USA

Hutton, M
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机构: Mayo Clin Jacksonville, Jacksonville, FL 32224 USA

Younkin, SG
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机构: Mayo Clin Jacksonville, Jacksonville, FL 32224 USA