McCarron M O, Nicoll J A, Stewart J, Ironside J W, Mann D M, Love S, Graham D I, Dewar D
Department of Neuropathology, Institute of Neurological Sciences, Southern General Hospital, Glasgow, United Kingdom.
J Neuropathol Exp Neurol. 1999 Jul;58(7):711-8. doi: 10.1097/00005072-199907000-00005.
Cerebral amyloid angiopathy (CAA) is associated with apolipoprotein E (APOE gene, apoE protein) polymorphism: current evidence suggests that the epsilon4 allele is a risk factor for the development of CAA and the epsilon2 allele predisposes to hemorrhage. We sought to determine the relationship between the APOE epsilon2 allele and both the immunoreactivity profiles and vascular complications of CAA. We performed immunohistochemistry for amyloid beta-protein (A beta), apoE, cystatin C, and activated microglia, and examined the morphology of cortical and leptomeningeal vessels in 37 CAA-related hemorrhage (CAAH), 26 Alzheimer disease (AD) patients, and 20 controls. The extent of immunostaining of vessels for A beta, apoE, cystatin C, and perivascular activated microglia increased from controls through AD to a maximum in CAAH patients. Among cases with CAA (37 CAAH, 19 AD, and 6 controls, n = 62) vascular apoE (p < 5 x 10(-4)), cystatin C (p < 10(-4)), activated microglia (p < 10(-4)), vessels with a high ratio of wall thickness to lumen diameter (p < 0.003) as well as dilated/microaneurysmal vessels (p < 0.01) were present more frequently in patients with hemorrhage than without; however, these features were not associated with the APOE epsilon2 allele. Fibrinoid necrosis alone was associated with the APOE epsilon2 allele (p < 0.04) and we suggest that over-representation of APOE epsilon2 in CAAH may result from its association with fibrinoid necrosis.
脑淀粉样血管病（CAA）与载脂蛋白E（APOE基因，载脂蛋白E蛋白）多态性相关：目前的证据表明，ε4等位基因是CAA发生发展的危险因素，而ε2等位基因易导致出血。我们试图确定APOE ε2等位基因与CAA的免疫反应谱及血管并发症之间的关系。我们对37例CAA相关性出血（CAAH）患者、26例阿尔茨海默病（AD）患者和20例对照进行了β淀粉样蛋白（Aβ）、载脂蛋白E、胱抑素C和活化小胶质细胞的免疫组织化学检测，并检查了皮质和软脑膜血管的形态。从对照组到AD患者再到CAAH患者，血管对Aβ、载脂蛋白E、胱抑素C和血管周围活化小胶质细胞的免疫染色程度逐渐增加。在CAA患者（37例CAAH、19例AD和6例对照，n = 62）中，血管载脂蛋白E（p < 5×10⁻⁴）、胱抑素C（p < 10⁻⁴）、活化小胶质细胞（p < 10⁻⁴）、壁厚与管腔直径比值高的血管（p < 0.003）以及扩张/微动脉瘤样血管（p < 0.01）在出血患者中比未出血患者更常见；然而，这些特征与APOE ε2等位基因无关。单独的纤维蛋白样坏死与APOE ε2等位基因相关（p < 0.04），我们认为CAAH中APOE ε2的过度表达可能是由于其与纤维蛋白样坏死的关联。
