Faculty of Pharmacy, Laval University, Quebec, QC, Canada.
CHU de Quebec Research Center, 2705, Boulevard Laurier, Room T2-05, Québec, QC, G1V 4G2, Canada.
Acta Neuropathol Commun. 2023 Oct 2;11(1):159. doi: 10.1186/s40478-023-01647-1.
Cognitive decline due to Alzheimer's disease (AD) is frequent in the geriatric population, which has been disproportionately affected by the COVID-19 pandemic. In this study, we investigated the levels of angiotensin-converting enzyme 2 (ACE2), a regulator of the renin-angiotensin system and the main entry receptor of SARS-CoV-2 in host cells, in postmortem parietal cortex samples from two independent AD cohorts, totalling 142 persons. Higher concentrations of ACE2 protein (p < 0.01) and mRNA (p < 0.01) were found in individuals with a neuropathological diagnosis of AD compared to age-matched healthy control subjects. Brain levels of soluble ACE2 were inversely associated with cognitive scores (p = 0.02) and markers of pericytes (PDGFRβ, p = 0.02 and ANPEP, p = 0.007), but positively correlated with concentrations of soluble amyloid-β peptides (Aβ) (p = 0.01) and insoluble phospho-tau (S396/404, p = 0.002). However, no significant differences in ACE2 were observed in the 3xTg-AD mouse model of tau and Aβ neuropathology. Results from immunofluorescence and Western blots showed that ACE2 protein is predominantly localized in microvessels in the mouse brain whereas it is more frequently found in neurons in the human brain. The present data suggest that higher levels of soluble ACE2 in the human brain may contribute to AD, but their role in CNS infection by SARS-CoV-2 remains unclear.
阿尔茨海默病（AD）导致的认知能力下降在老年人群中很常见，而老年人受到 COVID-19 大流行的影响尤为严重。在这项研究中，我们研究了血管紧张素转换酶 2（ACE2）在两个独立的 AD 队列的死后顶叶皮质样本中的水平，这两个队列共包含 142 人。ACE2 蛋白（p<0.01）和 mRNA（p<0.01）在具有 AD 病理诊断的个体中的浓度较高，与年龄匹配的健康对照组相比。可溶性 ACE2 的脑水平与认知评分呈负相关（p=0.02），与周细胞标志物（PDGFRβ，p=0.02 和 ANPEP，p=0.007）呈负相关，但与可溶性淀粉样β肽（Aβ）（p=0.01）和不溶性磷酸化 tau（S396/404，p=0.002）呈正相关。然而，在 tau 和 Aβ 神经病理学的 3xTg-AD 小鼠模型中，ACE2 没有观察到显著差异。免疫荧光和 Western blot 的结果表明，ACE2 蛋白主要在小鼠大脑的微血管中定位，而在人类大脑中则更频繁地在神经元中发现。目前的数据表明，人类大脑中可溶性 ACE2 水平较高可能与 AD 有关，但它们在中枢神经系统感染 SARS-CoV-2 中的作用尚不清楚。
