BACE1 levels by APOE genotype in non-demented and Alzheimer's post-mortem brains.
BACE1 levels by APOE genotype in non-demented and Alzheimer's post-mortem brains.
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DOI：
10.2174/1567205011310030010
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发表时间：
2013-03
影响因子：
2.1
通讯作者：
Sabbagh MN
中科院分区：
文献类型：
--
作者：
Decourt B;Gonzales A;Beach TG;Malek-Ahmadi M;Walker A;Sue L;Walker DG;Sabbagh MN
APOE基因型是阿尔茨海默病（AD）的已知易感因素。很明显，APOE ε4等位基因的存在增加了AD的发病风险，降低了AD的发病年龄，并可能影响AD的病理负担。在这项研究中，我们询问了AD和非痴呆（ND）大脑中的BACE 1水平是否因APOE基因型而不同。我们从尸检的AD和ND患者中分离出APOE ε3/3、ε3/4、ε4/4携带者的额中皮层（MFC）和颞中皮层（MTC）。所有AD受试者均符合NINDS-ADRDA和NIA-Reagan诊断AD的标准。将MFC和MTC均质化，并对裂解物进行ELISA和Western印迹以检测BACE 1。ELISA显示，总BACE 1水平较低，在MFC的AD相比，ND受试者。此外，在APOE ε4携带者中，ND额叶皮质中BACE 1水平低于ε3/3携带者。在AD MFC以及ND和AD MTC组织中未观察到BACE 1水平的差异。ELISA结果经Western blotting证实。我们的数据表明，脑BACEl水平可能受AD发病前载脂蛋白E基因型的影响，为ND和AD受试者CSF中淀粉样蛋白β 42水平较低提供了另一种解释。
The APOE genotype is a known susceptibility factor for Alzheimer’s disease (AD). It is apparent that the presence of the APOE ε4 allele increases the risk for developing AD, lowers the age of onset in AD, and may influence the pathological burden seen in AD. In this study, we asked whether BACE1 levels differ by APOE genotype in the AD and non-demented (ND) brain. We isolated mid-frontal cortex (MFC) and mid-temporal cortex (MTC) from postmortem ND and AD subjects that were APOE ε3/3, ε3/4, ε4/4 carriers. All AD subjects met NINDS-ADRDA and NIA-Reagan criteria for a diagnosis of AD. The MFC and MTC were homogenized and the lysates underwent ELISA and Western blotting for BACE1. The ELISA revealed that total BACE1 levels were lower in the MFC of AD compared to ND subjects. Furthermore, in APOE ε4 carriers BACE1 levels were lower than ε3/3 carriers in the ND frontal cortex. No difference in BACE1 levels was observed in AD MFC and in ND and AD MTC tissues. The ELISA results were confirmed by Western blotting. Our data suggest that brain BACEl levels may be influenced by the apolipoprotein E genotype before the onset of AD, providing an alternative explanation for the lower amyloid beta 42 levels in CSF in ND and AD subjects.