Hemming Matthew L, Selkoe Dennis J, Farris Wesley
Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Neurobiol Dis. 2007 Apr;26(1):273-81. doi: 10.1016/j.nbd.2007.01.004. Epub 2007 Jan 25.
Genetic and pathologic studies have associated angiotensin-converting enzyme (ACE) with Alzheimer disease. Previously, we and others have reported that ACE degrades in vitro the amyloid beta-protein (Abeta), a putative upstream initiator of Alzheimer disease. These studies support the hypothesis that deficiency in ACE-mediated Abeta proteolysis could increase Alzheimer disease risk and raise the question of whether ACE inhibitors, a commonly prescribed class of anti-hypertensive medications, can elevate Abeta levels in vivo. To test this hypothesis, we administered the ACE inhibitor captopril to two lines of APP transgenic mice harboring either low levels of Abeta or high levels of Abeta with associated plaque deposition. In both models, we show that captopril does not affect cerebral Abeta levels in either soluble or insoluble pools. Furthermore, we find no change in plaque deposition or in peripheral Abeta levels. Data from these Alzheimer models suggest that captopril and similar ACE inhibitors do not cause Abeta accumulation in vivo.
遗传和病理学研究已将血管紧张素转换酶（ACE）与阿尔茨海默病联系起来。此前，我们和其他人曾报道，ACE在体外可降解淀粉样β蛋白（Aβ），这是一种被认为是阿尔茨海默病上游启动因子的物质。这些研究支持这样一种假说，即ACE介导的Aβ蛋白水解功能缺陷可能会增加患阿尔茨海默病的风险，并引发了一个问题，即常用的一类抗高血压药物ACE抑制剂是否会在体内升高Aβ水平。为了验证这一假说，我们给两株APP转基因小鼠施用了ACE抑制剂卡托普利，这两株小鼠分别具有低水平的Aβ或高水平的Aβ以及相关的斑块沉积。在这两种模型中，我们都表明卡托普利对可溶性或不可溶性池中的脑Aβ水平均无影响。此外，我们发现斑块沉积或外周Aβ水平没有变化。来自这些阿尔茨海默病模型的数据表明，卡托普利和类似的ACE抑制剂不会在体内导致Aβ积累。
