Identification of a stable fragment of the Alzheimer amyloid precursor containing the beta-protein in brain microvessels.
Identification of a stable fragment of the Alzheimer amyloid precursor containing the beta-protein in brain microvessels.
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鉴定脑微血管中含有 β 蛋白的阿尔茨海默病淀粉样蛋白前体的稳定片段。
DOI：
10.1073/pnas.89.4.1345
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发表时间：
1992
影响因子：
11.1
通讯作者：
Selkoe,DJ
中科院分区：
文献类型：
--
作者：
Tamaoka,A;Kalaria,RN;Lieberburg,I;Selkoe,DJ
β -淀粉样蛋白前体蛋白（β APP）的蛋白水解改变导致大约40个残基淀粉样蛋白（A β P）的释放，这可能是阿尔茨海默病的一个精液发病事件。使用区域特异性β APP抗体，我们在脑组织中寻找含有完整A β P区域的稳定蛋白水解中间体。在从大脑皮层和其他脑区纯化的微血管中选择性地检测到22 kda β APP片段。在免疫印迹上，22 kda带被5种不同的β - APP羧基末端肽的抗血清和A - β - P区侧翼的重组蛋白β APP444-592和β APP592-695的亲和纯化抗体标记。这种蛋白质在全脑匀浆或无微血管的脑组织中几乎检测不到。该蛋白可从Triton X-100和其他洗涤剂中的微血管中提取，表明其与膜相关。与皮质微血管相比，从白质、小脑和非神经组织中纯化的微血管含有较少的22 kda蛋白。这种蛋白质存在于正常和阿尔茨海默病大脑的微血管中，在新鲜牛大脑的微血管中含量很低。22kda蛋白的大小和特异性免疫反应性表明，它是含有完整a β P的β APP的稳定片段。这种潜在的淀粉样变性中间体在微血管中的发生与阿尔茨海默病中一些a β P沉积的血管或血液起源一致。
Altered proteolysis of the beta-amyloid precursor protein (beta APP) resulting in release of the approximately 40-residue amyloid beta-protein (A beta P) may be a seminal pathogenetic event in Alzheimer disease. Using region-specific beta APP antibodies, we searched for stable proteolytic intermediates containing the intact A beta P region in brain tissue. A 22-kDa beta APP fragment was selectively detected in microvessels purified from cerebral cortex and other brain regions. On immunoblots, the 22-kDa band is labeled by five distinct antisera to beta APP carboxyl-terminal peptides and by affinity-purified antibodies to the recombinant proteins beta APP444-592 and beta APP592-695, which flank the A beta P region. The protein is virtually undetectable in whole-brain homogenates or microvessel-free fractions of brain. The protein is extractable from microvessels in Triton X-100 and other detergents, indicating its membrane association. In comparison with cortical microvessels, microvessels purified from white matter, cerebellum, and nonneural tissues contain lower amounts of the 22-kDa protein. The protein is found in microvessels of both normal and Alzheimer disease brains and occurs in low amounts in microvessels from fresh bovine brain. The size and specific immunoreactivity of the 22-kDa protein indicate that it is a stable fragment of beta APP containing the intact A beta P. The occurrence of this potentially amyloidogenic intermediate in microvessels is consistent with a vascular or hematogenous origin for some A beta P deposits in Alzheimer disease.