Wang Z Z, Jensson O, Thorsteinsson L, Vinters H V
Department of Pathology & Laboratory Medicine, UCLA Medical Center 90095-1732, USA.
APMIS. 1997 Jan;105(1):41-7. doi: 10.1111/j.1699-0463.1997.tb00538.x.
Hereditary cystatin C amyloid angiopathy (HCCAA), an autosomal dominant form of cerebral amyloid angiopathy (CAA) occurring primarily in Iceland, is characterized by a variant cystatin C amyloid deposition in the walls of cerebral parenchymal and leptomeningeal vessels. Cystatin C is also found to colocalize with amyloid beta/A4 protein in cerebral vessel walls of patients with Alzheimer's disease (AD), sporadic CAA, and hereditary cerebral hemorrhage with amyloidosis, Dutch type (HCHWA-D). The abundance of cystatin C deposition in cerebral blood vessel walls suggests that cellular elements of the vessel wall itself may play a role in its deposition. Microvascular changes in the brains of HCCAA patients were investigated by single- and double-label immunohistochemistry. We found that cystatin C amyloid immunoreactivity was present not only in cerebral cortical and leptomeningeal vessels, but also in white matter parenchymal vessels. Cystatin C deposition was more prominent in the media of parenchymal vessels and in the adventitia of leptomeningeal vessels. Smooth muscle (sm) cells were few or could not be identified within vessel walls showing extensive cystatin C deposition, suggesting progressive loss of these cells as cystatin C accumulates. However, in less severely affected vessels, cystatin C was present in cells that also had the phenotype of sm, suggesting that sm cells synthesize or process cystatin C. Cystatin C immunoreactivity was in addition, detected in some neuronal cell bodies throughout the cortex in patients with HCCAA and AD-related CAA. Our results indicate that cellular components of the vessel walls may play an important role in cystatin C deposition, as they do in beta/A4 deposition in AD-related CAA. Cystatin C deposition within the vascular media and adventitia, with associated vessel wall injury as manifested by sm cell loss, represents microvascular degeneration that leads to cerebral hemorrhage.
遗传性胱抑素C淀粉样血管病（HCCAA）是主要发生在冰岛的一种常染色体显性遗传性脑淀粉样血管病（CAA），其特征是在脑实质和软脑膜血管壁中有变异型胱抑素C淀粉样沉积。在阿尔茨海默病（AD）、散发性CAA以及荷兰型遗传性脑出血伴淀粉样变性（HCHWA-D）患者的脑血管壁中，也发现胱抑素C与β-淀粉样蛋白/A4蛋白共定位。脑血管壁中胱抑素C沉积丰富，提示血管壁本身的细胞成分可能在其沉积过程中发挥作用。通过单标记和双标记免疫组织化学方法研究了HCCAA患者大脑中的微血管变化。我们发现胱抑素C淀粉样免疫反应不仅存在于大脑皮质和软脑膜血管中，也存在于白质实质血管中。胱抑素C沉积在实质血管的中膜和软脑膜血管的外膜更为明显。在显示广泛胱抑素C沉积的血管壁内，平滑肌（sm）细胞很少或无法识别，提示随着胱抑素C的积累，这些细胞逐渐丢失。然而，在受影响较轻的血管中，胱抑素C存在于也具有sm表型的细胞中，提示sm细胞合成或加工胱抑素C。此外，在HCCAA和AD相关CAA患者的整个皮质的一些神经元细胞体中也检测到胱抑素C免疫反应。我们的结果表明，血管壁的细胞成分可能在胱抑素C沉积中起重要作用，就像它们在AD相关CAA的β/A4沉积中所起的作用一样。血管中膜和外膜内的胱抑素C沉积，以及伴随的以sm细胞丢失为表现的血管壁损伤，代表了导致脑出血的微血管退变。
