继发感染使大脑发炎，恶化阿尔茨海默病的认知
对阿尔茨海默病 (AD) 的新研究表明，继发性感染和新的炎症事件会放大大脑的免疫反应并影响小鼠和人类的记忆——即使这些继发性事件发生在大脑之外。
科学家们认为，由于 AD 引起的炎症，关键的脑细胞（星形胶质细胞和小胶质细胞）已经处于活跃状态，这项新研究表明，继发性感染会在这些细胞中引发过度反应，从而产生连锁反应。对大脑节律和认知的影响。
在这项刚刚发表在 阿尔茨海默病协会期刊Alzheimer’s & Dementia的研究中，经过改造以显示 AD 特征的小鼠暴露于急性炎症事件中，以观察对脑部炎症、神经元网络功能和记忆的下游影响。
这些小鼠的星形胶质细胞和小胶质细胞的输出出现了新的变化，并出现了新的认知障碍和扰乱的“脑节律”，这在健康、年龄匹配的小鼠中是没有的。这些新出现的认知变化类似于老年患者经常发生的谵妄等急性和令人痛苦的精神障碍。
尽管很难在患者身上复制这些发现，但该研究还表明，死于急性全身感染的 AD 患者的大脑中 IL-1β 水平升高，IL-1β 是一种促炎分子，对引起增强的免疫反应和新的免疫反应很重要。在 AD 小鼠中看到的起始中断。
三一生物化学与免疫学学院和三一生物医学科学研究所副教授 Colm Cunningham 领导了这项研究。他说：
Acute systemic inflammation exacerbates neuroinflammation in Alzheimer's disease: IL-1β drives amplified responses in primed astrocytes and neuronal network dysfunction
Abstract
Neuroinflammation contributes to Alzheimer's disease (AD) progression. Secondary inflammatory insults trigger delirium and can accelerate cognitive decline. Individual cellular contributors to this vulnerability require elucidation. Using APP/PS1 mice and AD brain, we studied secondary inflammatory insults to investigate hypersensitive responses in microglia, astrocytes, neurons, and human brain tissue. The NLRP3 inflammasome was assembled surrounding amyloid beta, and microglia were primed, facilitating exaggerated interleukin-1β (IL-1β) responses to subsequent LPS stimulation. Astrocytes were primed to produce exaggerated chemokine responses to intrahippocampal IL-1β. Systemic LPS triggered microglial IL-1β, astrocytic chemokines, IL-6, and acute cognitive dysfunction, whereas IL-1β disrupted hippocampal gamma rhythm, all selectively in APP/PS1 mice. Brains from AD patients with infection showed elevated IL-1β and IL-6 levels. Therefore, amyloid leaves the brain vulnerable to secondary inflammation at microglial, astrocytic, neuronal, and cognitive levels, and infection amplifies neuroinflammatory cytokine synthesis in humans. Exacerbation of neuroinflammation to produce deleterious outcomes like delirium and accelerated disease progression merits careful investigation in humans.