Trinity College Institute of Neuroscience, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland; School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
Neurobiol Aging. 2014 Jan;35(1):109-21. doi: 10.1016/j.neurobiolaging.2013.07.025. Epub 2013 Aug 29.
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by deposits of amyloid-β and neurofibrillary tangles. It has been suggested that inflammatory changes are associated with disease; however, it has not been established whether these are a consequence of ongoing neurodegeneration or whether inflammation itself contributes to disease pathogenesis. Recent studies suggest that exposure to infection can accelerate cognitive decline in AD patients, and pathogens have been detected in the AD brain. However, the influence of infection on neuroinflammation and pathology remains poorly understood. In this study, we examined the effect of a peripheral infection on AD pathology in APP/PS1 mice. We found that, 8 weeks after infection with the Gram negative respiratory pathogen Bordetella pertussis, there was significant infiltration of IFNγ- and IL-17-producing T cells and NKT cells in older APP/PS1 mice. This was accompanied by increased glial activation and amyloid-β deposition. The data suggest that infection is a critical factor in the progression of AD, emphasising the importance of early diagnosis and treatment of infections in elderly individuals.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，其特征是淀粉样β和神经纤维缠结的沉积。有研究表明，炎症变化与疾病有关；然而，尚不确定这些变化是持续神经退行性变的结果，还是炎症本身导致了疾病的发病机制。最近的研究表明，感染会加速 AD 患者的认知能力下降，并且在 AD 大脑中已经检测到病原体。然而，感染对神经炎症和病理学的影响仍知之甚少。在这项研究中，我们研究了外周感染对 APP/PS1 小鼠 AD 病理学的影响。我们发现，在感染革兰氏阴性呼吸道病原体百日咳博德特氏菌 8 周后，老年 APP/PS1 小鼠中出现了大量产生 IFNγ 和 IL-17 的 T 细胞和 NKT 细胞浸润。这伴随着小胶质细胞激活和淀粉样β沉积的增加。数据表明，感染是 AD 进展的关键因素，强调了对老年人感染进行早期诊断和治疗的重要性。
