Departments of Geriatric Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, China.
Departments of Cardiology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, China.
J Alzheimers Dis. 2020;74(2):579-587. doi: 10.3233/JAD-191225.
Cardiovascular disorders, e.g., atherosclerosis and hypertension, increase susceptibility to neurodegenerative diseases, like dementia and Alzheimer's disease (AD), with undetermined mechanisms. Moreover, whether myocardial infarction (MI) may similarly increases occurrence of AD is unknown. In the current study, we performed a MI model in wild-type and AD-prone APP/PS1 mice and assessed the development of AD in these mice. We found that MI-treated mice of both wild-type and APP/PS1 behaved poorer in a social recognition test, the Morris water maze, and the plus-maze discriminative avoidance task, compared to sham-treated controls. Mechanistically, MI significantly increased the levels of reactive oxygen species, as well as increased deposition of amyloid-β peptide aggregates and phosphorylation of tau protein in mouse brain, two signature pathological features for AD. Moreover, the microglia in the MI-mice appeared to alter polarization to a more proinflammatory phenotype. Together, our data suggest that MI may be a predisposing factor for AD development.
心血管疾病，如动脉粥样硬化和高血压，会增加患神经退行性疾病（如痴呆和阿尔茨海默病）的易感性，但具体机制尚不清楚。此外，心肌梗死（MI）是否也会增加 AD 的发生尚不清楚。在本研究中，我们在野生型和 AD 易感 APP/PS1 小鼠中建立了 MI 模型，并评估了这些小鼠中 AD 的发生情况。我们发现，与假手术对照组相比，MI 处理的野生型和 APP/PS1 小鼠在社交识别测试、Morris 水迷宫和加迷宫辨别性回避任务中表现更差。在机制上，MI 显著增加了活性氧的水平，以及在小鼠大脑中淀粉样β肽聚集物和 tau 蛋白磷酸化的沉积增加，这是 AD 的两个标志性病理特征。此外，MI 小鼠中的小胶质细胞似乎向更具炎症表型的极化方向发生改变。总之，我们的数据表明，MI 可能是 AD 发展的一个易感因素。
