Progression of cerebral amyloid angiopathy:: Accumulation of amyloid-β40 in affected vessels
Progression of cerebral amyloid angiopathy:: Accumulation of amyloid-β40 in affected vessels
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DOI：
10.1097/00005072-199804000-00008
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发表时间：
1998-04-01
影响因子：
3.2
通讯作者：
Greenberg, SM
中科院分区：
文献类型：
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作者：
Alonzo, NC;Hyman, BT;Greenberg, SM
脑血管淀粉样沉积（脑淀粉样血管病，或CAA）通常无症状，但在晚期病例中，它们可导致血管破裂和出血。CAA的进展过程是通过比较无症状（“轻度”）CAA的死后大脑与出血相关疾病（“重度CAA”）的大脑来研究的。皮质和脑膜血管进行β-淀粉样蛋白免疫染色，并通过共聚焦显微镜和系统定量取样进行检查。我们关注2个定量参数：受淀粉样蛋白影响的血管比例（血管淀粉样蛋白播种的测量）和每个受影响血管的淀粉样蛋白量（现有病变生长的测量）。令人惊讶的是，轻度和重度CAA中受影响的皮质血管比例没有差异（0.29 vs 0.32，p = 0.65），但每个受累皮质血管中40个氨基酸形式的β-淀粉样蛋白面积增加（198.5 +/- 38.7 vs 455.8 +/- 100.9 μ m（2）/血管，p < 0.007）。载脂蛋白E β 4等位基因剂量的增加（从0到1到2个拷贝）也与每条血管淀粉样蛋白增加相关，而每种CAA严重程度中受影响血管的比例没有变化。这些发现表明，从无症状进展到晚期CAA反映了淀粉样蛋白在先前接种淀粉样蛋白的血管中的进行性积累，并且该过程被载脂蛋白E β 4选择性地增强。
Cerebrovascular deposits of amyloid (cerebral amyloid angiopathy, or CAA) are generally asymptomatic, but in advanced cases, they can lead to vessel rupture and hemorrhage. The process of progression in CAA was studied by comparison of postmortem brains with asymptomatic ("mild") CAA to brains with the form of the disease associated with hemorrhage ("severe CAA"). Cortical and meningeal vessels were immunostained for beta-amyloid and examined by confocal microscopy and by systematic quantitative sampling. We focused on 2 quantitative parameters: the proportion of vessels affected by amyloid (a measure of amyloid seeding of vessels) and the amount of amyloid per affected vessel (a measure of growth of existing lesions). Surprisingly, there was no difference between the proportion of affected cortical vessels in mild and severe CAA (0.29 vs 0.32, p = 0.65), but rather an increase in the area of the 40 amino acid form of beta-amyloid per affected cortical vessel (198.5 +/- 38.7 vs 455.8 +/- 100.9 mu m(2)/vessel, p < 0.007). Increasing doses (from 0 to 1 to 2 copies) of the apolipoprotein E epsilon 4 allele were also associated with greater amyloid per vessel without change in the proportion of affected vessels within each class of CAA severity. These findings suggest that progression from asymptomatic to advanced CAA reflects progressive accumulation of amyloid in vessels previously seeded with amyloid, and that this process is selectively enhanced by apolipoprotein E epsilon 4.