Miller D L, Papayannopoulos I A, Styles J, Bobin S A, Lin Y Y, Biemann K, Iqbal K
New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314.
Arch Biochem Biophys. 1993 Feb 15;301(1):41-52. doi: 10.1006/abbi.1993.1112.
The pathological findings of Alzheimer's disease include amyloid deposition in cerebral blood vessels and in senile plaques. Both deposits are known to include peptides 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 beta-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 beta-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 carboxyl-terminal 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.
阿尔茨海默病的病理发现包括脑血管和老年斑中的淀粉样蛋白沉积。已知这两种沉积物都包含含有共同序列的肽。两种形式的淀粉样蛋白都被分离出来，并确定了它们的肽组成。这些肽通过在70%甲酸中的尺寸排阻色谱法以及在60%甲酸、0 - 40%乙腈中的反相色谱法进行分离。老年斑淀粉样核心含有约25%的蛋白质，其中约70%由含有β-淀粉样序列的肽组成。核心淀粉样肽（CAPs）的氨基末端测序显示出广泛的氨基末端异质性，有不同数量的封闭氨基末端。CAP混合物的基质辅助激光解吸飞行时间质谱分析揭示了一系列肽，其分子量对应于以β-肽序列的前11个氨基酸中的每一个开始并以该序列的Ala - 42结束的肽。通过胰凝乳蛋白酶消化产物的串联质谱法鉴定了羧基末端残基。CAP具有较小程度的羧基末端异质性。脑血管淀粉样肽（CVAPs）在氨基末端和羧基末端都具有较小程度的异质性。主要的CVAP从Asp - 1开始，到Val - 40结束。CAP的次要成分的分子量为8,000 - 9,000 Da，并且与CAP的主要成分具有相同的氨基末端残基。它们可能是较小CAPs的前体。CAPs和CVAPs在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通过不同的途径形成，在这些途径中它们遇到不同的蛋白酶。
