Lendon C L, Thaker U, Harris J M, McDonagh A M, Lambert J-C, Chartier-Harlin M-C, Iwatsubo T, Pickering-Brown S M, Mann D M A
Department of Psychiatry, University of Birmingham, Birmingham B15 2QZ, UK.
Neurosci Lett. 2002 Aug 16;328(3):314-8. doi: 10.1016/s0304-3940(02)00553-0.
An insertion (I)/deletion (D) polymorphism in the angiotensin 1-converting enzyme (ACE) gene has, in some studies, been associated with increased risk for Alzheimer's disease (AD), and functionally the enzyme has been implicated in the degradation of amyloid beta protein (Abeta). We have investigated the frequency of the I/D polymorphism in a clinic-based and autopsy-confirmed series of cases of AD, and investigated what impact the I/D polymorphism in ACE gene might have on the extent of Abeta and tau pathology in the frontal cortex in the autopsy-confirmed series. We found no differences in I/D allele or genotype frequencies between the clinic-based and autopsy-confirmed AD cases, or between the pooled clinic-based and autopsy-confirmed AD cases and a series of normal control subjects. Moreover, Abeta (Abeta(40) and Abeta(42)) load, tau load or extent of amyloid angiopathy did not differ between D/D, I/D and I/I genotype groups, though Abeta(42) load tended to be higher in bearers of I/I genotype (compared to D/D genotype). Neither age at onset nor duration of illness differed according to genotype. We conclude therefore that the frequency of ACE I-allele is not increased in AD and, in autopsy-confirmed AD cases, possession of the ACE I allele has no impact upon the pathology of AD, at least in terms of the amount of Abeta or tau deposited in the brain.
在一些研究中，血管紧张素转换酶（ACE）基因中的插入（I）/缺失（D）多态性与阿尔茨海默病（AD）风险增加有关，并且从功能上来说，该酶与淀粉样β蛋白（Aβ）的降解有关。我们调查了基于临床且经尸检确诊的AD病例系列中I/D多态性的频率，并研究了ACE基因中的I/D多态性对经尸检确诊系列中额叶皮质Aβ和tau病理程度可能产生的影响。我们发现，基于临床的AD病例与经尸检确诊的AD病例之间，以及汇总的基于临床和经尸检确诊的AD病例与一系列正常对照受试者之间，I/D等位基因或基因型频率没有差异。此外，D/D、I/D和I/I基因型组之间的Aβ（Aβ40和Aβ42）负荷、tau负荷或淀粉样血管病程度没有差异，尽管I/I基因型携带者的Aβ42负荷往往更高（与D/D基因型相比）。发病年龄和病程也不因基因型而异。因此，我们得出结论，AD中ACE I等位基因的频率并未增加，并且在经尸检确诊的AD病例中，至少就大脑中沉积的Aβ或tau的量而言，携带ACE I等位基因对AD的病理没有影响。
