β-secretase protein and activity are increased in the neocortex in Alzheimer disease
β-secretase protein and activity are increased in the neocortex in Alzheimer disease
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DOI：
10.1001/archneur.59.9.1381
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发表时间：
2002-09-01
影响因子：
--
通讯作者：
Irizarry, MC
中科院分区：
文献类型：
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作者：
Fukumoto, H;Cheung, BS;Irizarry, MC
背景：淀粉样斑块是阿尔茨海默病（AD）的主要病理特征，由淀粉样前体蛋白（APP）的内部片段组成：4-kd淀粉样β蛋白（Abeta）。APP的代谢过程导致β的形成需要2个酶裂解事件，一个依赖于早老素的γ -分泌酶裂解，以及一个由天冬氨酸蛋白酶β位点APP裂解酶（BACE）裂解的β -分泌酶裂解。目的：验证阿尔茨海默病患者脑内淀粉样斑块区BACE蛋白和活性升高的假说。方法：我们开发了一种抗体捕获系统来测量61例AD患者和33例对照脑的额叶、颞叶和小脑匀浆中BACE蛋白水平和BACE特异性β -分泌酶活性。结果：AD大鼠脑内BACE活性及蛋白水平显著升高(P
Context: Amyloid plaques, a major pathological feature of Alzheimer disease (AD), are composed of an internal fragment of amyloid precursor protein (APP): the 4-kd amyloid-beta protein (Abeta). The metabolic processing of APP that results in Abeta formation requires 2 enzymatic cleavage events, a gamma-secretase cleavage dependent on presenilin, and a beta-secretase cleavage by the aspartyl protease beta-site APP-cleaving enzyme (BACE).Objective: To test the hypothesis that BACE protein and activity are increased in regions of the brain that develop amyloid plaques in AD.Methods: We developed an antibody capture system to measure BACE protein level and BACE-specific beta-secretase activity in frontal, temporal, and cerebellar brain homogenates from 61 brains with AD and 33 control brains.Results: In the brains with AD, BACE activity and protein were significantly increased (P