ADAM10 expression and promoter haplotype in Alzheimer's disease.
ADAM10 expression and promoter haplotype in Alzheimer's disease.
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DOI：
10.1016/j.neurobiolaging.2012.03.013
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发表时间：
2012-09
影响因子：
4.2
通讯作者：
Yu CE
中科院分区：
文献类型：
--
作者：
Bekris LM;Lutz F;Li G;Galasko DR;Farlow MR;Quinn JF;Kaye JA;Leverenz JB;Tsuang DW;Montine TJ;Peskind ER;Yu CE
根据脑神经炎斑块和神经纤维缠结在脑中的积累，在尸检中证实阿尔茨海默病。神经炎斑块含有Aβ，Aβ水平降低对应于ADAM 10 α-分泌酶活性增加。ADAM 10 α-分泌酶活性产生可溶性APP α（sAPPα）产物，并消除Aβ的病理性产生。在本研究中，假设ADAM 10启动子的遗传变异与ADAM 10表达水平以及CSF sAPPα水平相关。本研究结果表明，ADAM 10 rs 514049-rs653765 C-A启动子单倍型与：1）与AD相比，认知正常对照组的CSF sAPPα水平较高，2）死后脑海马较高，但小脑不较高，与高斑块评分受试者相比，低斑块评分受试者中的ADAM 10蛋白水平，以及3）在人神经母细胞瘤SHSY 5 Y细胞系中，仅启动子报告基因构建体的启动子活性高于启动子3 'UTR构建体，但在HepG 2或U118细胞系中则不然。综上所述，这些发现表明，ADAM 10的表达是根据一个启动子单倍型，在大脑区域和细胞类型的特定方式的影响。
Alzheimer’s disease is confirmed at autopsy according to the accumulation of brain neuritic plaques and neurofibrillary tangles in the brain. Neuritic plaques contain Aβ and lower levels of Aβ correspond to an increase in ADAM10 α-secretase activity. ADAM10 α-secretase activity produces a soluble APP alpha (sAPPα) product and negates the pathological production of Aβ. In this investigation it was hypothesized that genetic variation with the ADAM10 promoter is associated with ADAM10 expression levels as well as CSF sAPPα levels. Results from this investigation suggest that the ADAM10 rs514049–rs653765 C-A promoter haplotype is associated with; 1) higher CSF sAPPα levels in cognitively normal controls compared to AD, 2) higher post mortem brain hippocampus, but not cerebellum, ADAM10 protein levels in low plaque score subjects compared to high plaque score subjects and 3) higher promoter activity for promoter only reporter constructs compared to promoter – 3′UTR constructs in the human neuroblastoma SHSY5Y cell line, but not in HepG2 or U118 cell lines. Taken together, these findings suggest that ADAM10 expression is modulated according to a promoter haplotype that is influenced in a brain region and cell type specific manner.
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影响因子：
4.8
作者：
Lammich, Sven;Buell, Dominik;Haass, Christian
通讯作者：
Haass, Christian
DOI：
10.1097/01.wad.0000194014.43575.fd
发表时间：
2005-10-01
影响因子：
2.1
作者：
Peskind, ER;Riekse, R;Galasko, D
通讯作者：
Galasko, D
影响因子：
4.2
作者：
Bekris LM;Galloway NM;Millard S;Lockhart D;Li G;Galasko DR;Farlow MR;Clark CM;Quinn JF;Kaye JA;Schellenberg GD;Leverenz JB;Seubert P;Tsuang DW;Peskind ER;Yu CE
通讯作者：
Yu CE
影响因子：
3.5
作者：
Kim, Minji;Suh, Jaehong;Tanzi, Rudolph E.
通讯作者：
Tanzi, Rudolph E.
影响因子：
14.9
作者：
Rosenbloom KR;Dreszer TR;Long JC;Malladi VS;Sloan CA;Raney BJ;Cline MS;Karolchik D;Barber GP;Clawson H;Diekhans M;Fujita PA;Goldman M;Gravell RC;Harte RA;Hinrichs AS;Kirkup VM;Kuhn RM;Learned K;Maddren M;Meyer LR;Pohl A;Rhead B;Wong MC;Zweig AS;Haussler D;Kent WJ
通讯作者：
Kent WJ