Cerebral amyloid angiopathy: major contributor or decorative response to Alzheimer's disease pathogenesis
Cerebral amyloid angiopathy: major contributor or decorative response to Alzheimer's disease pathogenesis
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DOI：
10.1016/j.neurobiolaging.2003.12.019
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发表时间：
2004-05-01
影响因子：
4.2
通讯作者：
Friedland, RP
中科院分区：
文献类型：
--
作者：
Castellani, RJ;Smith, MA;Friedland, RP
脑血管内淀粉样蛋白沉积或脑淀粉样血管病（CAA）在老年人中很常见，在阿尔茨海默病中更为常见。CAA可能并发大叶性脑出血，而罕见的常染色体显性CAA也表现出脑出血的倾向，这是由于特定淀粉样蛋白的种系突变和明显的淀粉样蛋白沉积导致血管壁结构完整性明显受损。然而，脑淀粉样血管病与认知功能障碍之间的关系尚不清楚。虽然家族性CAA的认知功能障碍可能与大量淀粉样蛋白沉积和血管腔损伤有关（例如，遗传性脑出血伴血管病变-荷兰型（HCHWA-D）），但脑淀粉样蛋白血管病变伴脑出血在认知完整的老年患者中经常零星出现。此外，虽然约80%的阿尔茨海默病患者在尸检时血管壁内有明显的β淀粉样蛋白，但绝大多数患者在生活中没有出现临床相关的脑出血。剩下的20%的患者在血管内几乎没有淀粉样蛋白的情况下进展并死于疾病。因此，在散发性晚发性阿尔茨海默病和CAA中，β淀粉样蛋白沉积在脑血管中的作用，一方面与认知功能有关，另一方面与出血倾向有关，仍有待解决。最近对转基因APP23小鼠的研究表明，被动免疫与淀粉样血管病相关脑出血之间存在关系，尽管目前的数据尚不清楚出血的机制。我们认为淀粉样蛋白积累代表了对慢性应激的反应，神经退行性过程发生在神经元水平，包括氧化应激和异常细胞周期激活。因此，CAA代表组织内稳态，因此这种平衡的突然扰动（例如，淀粉样蛋白P免疫）是有害的。(C) 2004出版的爱思唯尔公司。
Amyloid deposition within cerebral vessels, or cerebral amyloid angiopathy (CAA), is common in advanced age and even more common in Alzheimer's disease. CAA may be complicated by lobar intracerebral hemorrhage, while rare kindreds of autosomal dominant CAA also show propensity for intracerebral hemorrhage, due to germline mutations in specific amyloidogenic precursor proteins and apparent compromise of structural integrity of the blood vessel wall due to marked amyloid deposition. The relationship between cerebral amyloid angiopathy and cognitive dysfunction, however, is less clear. While cognitive dysfunction in familial CAA is likely related to prodigious amyloid deposits and vascular luminal compromise (e.g., hereditary cerebral hemorrhage with angiopathy-Dutch type (HCHWA-D)), cerebral amyloid angiopathy with intracerebral hemorrhage often presents sporadically in cognitively intact elderly patients. Moreover, while about 80% of subjects with Alzheimer's disease have demonstrable amyloid beta within blood vessel walls at autopsy, the vast majority of these fail to suffer clinically relevant intracerebral hemorrhage during life. The remaining 20% manage to progress and die of their disease with virtual no amyloid within blood vessels. Thus, the role of amyloid beta deposits in cerebral vessels as regards cognitive function on the one hand, and tendency for hemorrhage on the other, remain to be resolved for sporadic late onset Alzheimer's disease and CAA. Recent studies on transgenic APP23 mice suggest a relationship between passive immunization and amyloid angiopathy-associated cerebral hemorrhage, although the mechanism of hemorrhage was unclear from the data presented. We suggest that amyloid accumulation represents a response to chronic stress, and that the neurodegenerative process occurs at the neuronal level, encompassing oxidative stress and aberrant cell cycle activation. As such, CAA represents tissue homeostasis, such that an abrupt perturbation of this balance (e.g., amyloid P immunization) is deleterious. (C) 2004 Published by Elsevier Inc.