Dementia Research Group, Clinical Neurosciences, Bristol Medical School, University of Bristol, Learning and Research Building, Southmead Hospital, Bristol, UK.
J Gerontol A Biol Sci Med Sci. 2022 Sep 1;77(9):1775-1783. doi: 10.1093/gerona/glac083.
An imbalance in the renin-angiotensin system (RAS) is associated with cognitive decline and disease pathology in Alzheimer's disease (AD). In this study, we have investigated changes in the brain angiotensin-converting enzyme-1 (ACE-1) and angiotensin-II (Ang-II), and the counter-regulatory angiotensin-converting enzyme-2 (ACE-2), in the frontal and temporal cortex during normal aging and in the early stages of AD. We studied a cohort of normal aging (n = 121; 19-95 years age-at-death) from the Sudden Death Brain Bank, University of Edinburgh, United Kingdom, and AD and age-matched controls (n = 60) from the South West Dementia Brain Bank, University of Bristol, United Kingdom, stratified according to Braak tangle stage (BS): 0-II, III-IV (intermediate disease), and V-VI (end-stage disease). ACE-1 and ACE-2 enzyme activity were measured using fluorogenic peptide activity assays. ACE-1, ACE-2, and Ang-II protein level were measured by enzyme-linked immunosorbent assay (ELISA). In both regions, ACE-1 protein and Ang-II levels correlated positively with age whereas ACE-1 enzyme activity was inversely related to age. ACE-1 protein correlated positively with Ang-II, whilst ACE-1 activity correlated inversely with Ang-II in normal aging. ACE-1 enzyme activity was elevated at an early/intermediate stage, BS III-IV compared to BS 0-II in the temporal cortex in AD. ACE-2 protein and enzyme activity were unchanged with aging and in AD. In conclusion, ACE-1 activity is induced in the early stages of AD independently from normal physiological age-related changes in ACE-1 protein.
肾素-血管紧张素系统（RAS）失衡与阿尔茨海默病（AD）中的认知能力下降和疾病病理有关。在这项研究中，我们研究了在正常衰老和 AD 的早期阶段，大脑血管紧张素转换酶-1（ACE-1）和血管紧张素-II（Ang-II）以及代偿性血管紧张素转换酶-2（ACE-2）在额颞叶皮质中的变化。我们研究了来自英国爱丁堡大学猝死脑库的正常衰老队列（n = 121；死亡时年龄为 19-95 岁）和来自英国布里斯托尔大学西南痴呆脑库的 AD 和年龄匹配的对照组（n = 60），根据 Braak 缠结阶段（BS）进行分层：0-II、III-IV（中间疾病）和 V-VI（终末期疾病）。使用荧光肽活性测定法测量 ACE-1 和 ACE-2 酶活性。通过酶联免疫吸附测定法（ELISA）测量 ACE-1、ACE-2 和 Ang-II 蛋白水平。在两个区域中，ACE-1 蛋白和 Ang-II 水平与年龄呈正相关，而 ACE-1 酶活性与年龄呈负相关。在正常衰老中，ACE-1 蛋白与 Ang-II 呈正相关，而 ACE-1 活性与 Ang-II 呈负相关。与 BS 0-II 相比，AD 患者颞叶皮质中 BS III-IV 时 ACE-1 酶活性在早期/中期升高。ACE-2 蛋白和酶活性在衰老和 AD 中无变化。总之，ACE-1 活性在 AD 的早期阶段被诱导，与 ACE-1 蛋白的正常生理年龄相关变化无关。
