BETA-AMYLOID-(1-42) IS A MAJOR COMPONENT OF CEREBROVASCULAR AMYLOID DEPOSITS - IMPLICATIONS FOR THE PATHOLOGY OF ALZHEIMER-DISEASE
BETA-AMYLOID-(1-42) IS A MAJOR COMPONENT OF CEREBROVASCULAR AMYLOID DEPOSITS - IMPLICATIONS FOR THE PATHOLOGY OF ALZHEIMER-DISEASE
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DOI：
10.1073/pnas.90.22.10836
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发表时间：
1993-11-15
影响因子：
11.1
通讯作者：
BALL, MJ
中科院分区：
文献类型：
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作者：
ROHER, AE;LOWENSON, JD;BALL, MJ
对阿尔茨海默病大脑血管组织中β -淀粉样肽（Abeta）沉积物化学结构的重新研究表明，42-残基形式的Abeta-(1-42)，而不是更易溶解的Abeta-(1-40)形式，是主要的肽。用SDS和胶原酶去除周围组织后，Abeta在甲酸中溶解，并通过Superose - 12层析纯化。通过高效液相色谱法（HPLC）对酶解和化学消化产生的肽进行纯化，并通过氨基酸分析、序列分析和质谱分析对其进行了表征。在小脑膜血管中，β -(1-42)/ β -(1-40)的平均比值为58:42，而在实质血管中，这一比值为75:25。有趣的是，血管β比神经斑块β含有更少的异构化和外消旋化的天冬氨酸残基，这表明血管淀粉样蛋白“更年轻”。“分别与小动脉和毛细血管相关的带状和球形沉积物的离散性表明，这种淀粉样蛋白来自血管组织本身。增加Abeta沉积似乎导致毛细血管扭曲和闭塞，这可能对阿尔茨海默病的病理有重要贡献。
Reinvestigation of the chemical structure of beta-amyloid peptide (Abeta) deposits in the vascular tissue of Alzheimer disease brains revealed that the 42-residue form Abeta-(1-42), rather than the more soluble Abeta-(1-40) form, is the predominant peptide. Following removal of the surrounding tissue with SDS and collagenase, Abeta was solubilized in formic acid and purified by Superose 12 chromatography. Peptides generated by enzymatic and chemical digestion of the Abeta were purified by HPLC and characterized by amino acid analysis, sequence analysis, and mass spectrometry. In the leptomeningeal vessels, the average ratio of Abeta-(1-42)/Abeta-(1-40) was 58:42, whereas in the parenchymal vessels this ratio was 75:25. Interestingly, vascular Abeta contains considerably less isomerized and racemized aspartyl residues than does neuritic plaque Abeta, suggesting that the vascular amyloid is ''younger.'' The discrete nature of the bands and spherical deposits of Abeta associated with arterioles and capillaries, respectively, suggests that this amyloid arises from the vascular tissue itself. Increasing Abeta deposition appears to lead to the distortion and occlusion of capillaries, which may contribute significantly to the pathology of Alzheimer disease.