BETA-AMYLOID PRECURSOR PROTEIN OF ALZHEIMER-DISEASE OCCURS AS 110-KILODALTON TO 135-KILODALTON MEMBRANE-ASSOCIATED PROTEINS IN NEURAL AND NONNEURAL TISSUES
BETA-AMYLOID PRECURSOR PROTEIN OF ALZHEIMER-DISEASE OCCURS AS 110-KILODALTON TO 135-KILODALTON MEMBRANE-ASSOCIATED PROTEINS IN NEURAL AND NONNEURAL TISSUES
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DOI：
10.1073/pnas.85.19.7341
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发表时间：
1988-10-01
影响因子：
11.1
通讯作者：
OLTERSDORF, T
中科院分区：
文献类型：
--
作者：
SELKOE, DJ;PODLISNY, MB;OLTERSDORF, T
渐进性脑沉积细胞外细丝组成。-淀粉样蛋白（. β . ap）是阿尔茨海默病（AD）的一个恒定特征。因为21号染色体上的基因编码。AP前体（.beta. app）在AD中未被改变，转录或翻译后的变化可能是加速的基础。美联社沉积。使用两种抗体来预测β的羧基末端。APP，我们已经确认了原生测试版。APP存在于大脑和非神经组织中，是一种110- 135 kda的蛋白质复合物，不溶于缓冲液，存在于各种富含膜的亚细胞组分中。这些蛋白在成人大脑中分布相对均匀，在胎儿大脑中含量丰富，在含有β的非神经组织中也能检测到。应用mRNA。同样大小的蛋白存在于大鼠、牛和猴的大脑以及培养的人HL-60和HeLa细胞中；在110- 135kda范围内的精确模式在不同的组织和细胞系中是不均匀的。证实免疫检测到的组织蛋白是。β的形式。在哺乳动物细胞中转染全长. β。APP cDNA显示110- 135kda蛋白选择性扩增表达和特异性免疫细胞化学染色。出乎意料的是，抗体的羧基端。APP标记AD脑内含淀粉样老年斑。我们得出结论，高度保守的。APP分子存在于哺乳动物组织中，是一组异质性的膜相关蛋白。120 kDa。检测斑块内的非淀粉样蛋白羧基端表明。形成不溶性细丝的APP在发育β的皮质区域局部发生。-淀粉样蛋白随年龄增长而沉积。
Progressive cerebral deposition of extracellular filaments composed of the .beta.-amyloid protein (.beta.AP) is a constant feature of Alzheimer disease (AD). Since the gene on chromosome 21 encoding the .beta.AP precursor (.beta.APP) is not known to be altered in AD, transcriptional or posttranslational changes may underlie accelerated .beta.AP deposition. Using two antibodies to the predicted carboxyl terminus of .beta.APP, we have identified the native .beta.APP in brain and nonneural human tissues as a 110- to 135-kDa protein complex that is insoluble in buffer and found in various membrane-rich subcellular fractions. These proteins are relatively uniformly distributed in adult brain, abundant in fetal brain, and detected in nonneural tissues that contain .beta.APP mRNA. Similarly sized proteins occur in rat, cow, and monkey brain and in cultured human HL-60 and HeLa cells; the precise patterns in the 110- to 135-kDa range are heterogeneous among various tissues and cell lines. Confirmation that the immunodetected tissue proteins are forms of .beta.APP was obtained when mammalian cells transfected with a full-length .beta.APP cDNA showed selectively augmented expression of 110- to 135-kDa proteins and specific immunocytochemical staining. Unexpectedly, the antibodies to the carboxyl terminus of .beta.APP labeled amyloid-containing senile plaques in AD brain. We conclude that the highly conserved .beta.APP molecule occurs in mammalian tissues as a heterogeneous group of membrane-associated proteins of .apprxeq. 120 kDa. Detection of the nonamyloidogenic carboxyl terminus within plaques suggests that proteolytic processing of the .beta.APP into insoluble filaments occurs locally in cortical regions that develop .beta.-amyloid deposits with age.