Amyloid precursor protein (APP) processing genes and cerebrospinal fluid APP cleavage product levels in Alzheimer's disease.
Amyloid precursor protein (APP) processing genes and cerebrospinal fluid APP cleavage product levels in Alzheimer's disease.
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DOI：
10.1016/j.neurobiolaging.2010.10.020
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发表时间：
2011-03
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;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
本探索性研究的目的是确定认知正常受试者或阿尔茨海默病（AD）患者脑脊液（CSF）中APP或其加工酶内的遗传变异是否与APP裂解产物（APPα、APPβ或Aβ42）水平相关。认知正常的对照组（n=170）和AD患者（n=92）在参与APP加工途径的9个基因（APP、ADAM 10、BACE1、BACE2、PSEN1、PSEN2、PEN2、NCENTR和APH1B）内对19个推定的调控标签SNP进行基因分型。检测SNP基因型与CSF APPα、APPβ和Aβ42、AD风险和发病年龄的相关性，同时考虑年龄、性别、种族和APOE ε4。在调整多重比较后，发现ADAM10 SNP rs514049和APPα水平之间存在显著相关性。在对照组中，rs514049 CC基因型的APPα水平高于CA，AA塌陷基因型，而在AD患者中观察到相反的效果。这些结果表明，APP加工基因ADAM 10的遗传变异以AD特异性方式影响CSF APPα水平。
The aim of this exploratory investigation was to determine if genetic variation within APP or its processing enzymes correlates with APP cleavage product levels: APPα, APPβ or Aβ42, in cerebrospinal fluid (CSF) of cognitively normal subjects or Alzheimer’s disease (AD) patients. Cognitively normal control subjects (n=170) and AD patients (n=92) were genotyped for 19 putative regulatory tagging SNPs within nine genes (APP, ADAM10, BACE1, BACE2, PSEN1, PSEN2, PEN2, NCSTN and APH1B) involved in the APP processing pathway. SNP genotypes were tested for their association with CSF APPα, APPβ, and Aβ42, AD risk and age-at-onset while taking into account age, gender, race and APOE ε4. After adjusting for multiple comparisons a significant association was found between ADAM10 SNP rs514049 and APPα levels. In controls, the rs514049 CC genotype had higher APPα levels than the CA,AA collapsed genotype, whereas the opposite effect was seen in AD patients. These results suggest that genetic variationwithin ADAM10, an APP processing gene, influences CSF APPα levels in an AD specific manner.
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影响因子：
11
作者：
Alves, Guido;Bronnick, Kolbjorn;Mulugeta, Ezra
通讯作者：
Mulugeta, Ezra
影响因子：
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作者：
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DOI：
10.1073/pnas.96.7.3922
发表时间：
1999-03-30
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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