PEPTIDE COMPOSITIONS OF THE CEREBROVASCULAR AND SENILE PLAQUE CORE AMYLOID DEPOSITS OF ALZHEIMERS-DISEASE
PEPTIDE COMPOSITIONS OF THE CEREBROVASCULAR AND SENILE PLAQUE CORE AMYLOID DEPOSITS OF ALZHEIMERS-DISEASE
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DOI：
10.1006/abbi.1993.1112
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发表时间：
1993-02-15
影响因子：
3.9
通讯作者：
IQBAL, K
中科院分区：
文献类型：
--
作者：
MILLER, DL;PAPAYANNOPOULOS, IA;IQBAL, K
阿尔茨海默病*S病的病理表现包括脑血管和老年斑中的淀粉样沉积。众所周知，这两种沉积物都包括含有共同层序的潮汐。分离了两种形式的淀粉样蛋白，并测定了它们的多肽组成。用体积排阻层析法在70%的甲酸中拆分，用反相色谱在60%的甲酸、0-40%的乙腈中拆分。老年斑淀粉样蛋白核心含有约25%的蛋白质，其中约70%由含有β-淀粉样蛋白序列的多肽组成。核心淀粉样多肽(CAPs)的氨基末端测序显示了广泛的氨基末端异质性，具有不同数量的封闭的氨基末端。基质辅助的激光解吸飞行时间飞行时间质谱仪显示了一系列多肽，其分子量对应于从β-肽序列的前11个氨基酸开始到该序列的ALA-42结束的多肽。用凝乳酶消化后的串联质谱仪鉴定其羧基末端残基。CAP具有少量的羧基-末端异质性。脑血管淀粉样多肽(CVAP)具有轻微的氨基和羧基末端异质性。主要的CVAP开始于Asp-1，结束于Val-40。CAP的次要成分的质量为8000~9000 Da，与主要成分的氨基端残基相同。它们可能是小盘股的前身。CAPS和CVAP的氨基末端和羧基末端的差异表明，这两种类型的淀粉样蛋白是通过不同的途径形成的，它们在不同的途径上遇到了不同的蛋白酶。
The pathological findings of Alzheimer*s disease include amyloid deposition in cerebral blood vessels and in senile plaques. Both deposits are known to include pep-tides that contain a common sequence. Both forms of amyloid were isolated and their peptide compositions were determined. The peptides were resolved by size-exclusion chromatography in 70% formic acid, and reverse-phase chromatography in 60% formic acid, 0-40% acetonitrile. Senile plaque amyloid cores contain about 25% protein, about 70% of which is composed of peptides containing the β-amyloid sequence. Amino-terminal sequencing of the core amyloid peptides (CAPs) revealed extensive amino-terminal heterogeneity, with variable amounts of blocked amino termini. Matrix-assisted, laser-desorption-time-of-flight mass spectrometry of the CAP mixture revealed an array of peptides the molecular weights of which corresponded to peptides beginning with each of the first 11 amino acids of the β-peptide sequence and ending with Ala-42 of that sequence. The carboxyl-terminal residues were identified by tandem mass spectrometry of chymotrypsin digests. CAP possessed a minor degree of carboxyl-terminal heterogeneity. Cerebrovascular amyloid peptides (CVAPs) possessed minor degrees of both amino- and carboxylterminal heterogeneity. The major CVAP commenced at Asp-1 and ended at Val-40. Minor components of CAP possessed masses of 8000-9000 Da and the same amino terminal residues as the major components of CAP. They may be precursors to the smaller CAPs. The differences in amino termini and carboxyl termini of CAPs and CVAPs suggest that the two types of amyloid form by different pathways, on which they encounter different proteases.