McManus Róisín M, Heneka Michael T
German Center for Neurodegenerative Diseases (DZNE), Sigmund Freud Str. 27, 53127, Bonn, Germany.
Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology, University of Bonn Medical Center, Sigmund-Freud Str. 25, 53127, Bonn, Germany.
Alzheimers Res Ther. 2017 Mar 4;9(1):14. doi: 10.1186/s13195-017-0241-2.
Previously, the contribution of peripheral infection to cognitive decline was largely overlooked however, the past 15 years have established a key role for infectious pathogens in the progression of age-related neurodegeneration. It is now accepted that the immune privilege of the brain is not absolute, and that cells of the central nervous system are sensitive to both the inflammatory events occurring in the periphery and to the infiltration of peripheral immune cells. This is particularly relevant for the progression of Alzheimer's disease, in which it has been demonstrated that patients are more vulnerable to infection-related cognitive changes. This can occur from typical infectious challenges such as respiratory tract infections, although a number of specific viral, bacterial, and fungal pathogens have also been associated with the development of the disease. To date, it is not clear whether these microorganisms are directly related to Alzheimer's disease progression or if they are opportune pathogens that easily colonize those with dementia and exacerbate the ongoing inflammation observed in these individuals. This review will discuss the impact of each of these challenges, and examine the changes known to occur with age in the peripheral immune system, which may contribute to the age-related vulnerability to infection-induced cognitive decline.
以前，外周感染对认知衰退的影响在很大程度上被忽视了。然而，在过去的15年里，传染性病原体在与年龄相关的神经退行性变进展中的关键作用已得到确认。现在人们认识到，大脑的免疫特权并非绝对，中枢神经系统的细胞对外周发生的炎症事件以及外周免疫细胞的浸润均敏感。这对于阿尔茨海默病的进展尤为重要，在该病中已证实患者更容易出现与感染相关的认知变化。这可能源于典型的感染挑战，如呼吸道感染，尽管一些特定的病毒、细菌和真菌病原体也与该病的发展有关。迄今为止，尚不清楚这些微生物是否与阿尔茨海默病的进展直接相关，或者它们是否是容易在痴呆患者中定植并加剧这些个体中持续炎症的机会性病原体。本综述将讨论这些挑战各自的影响，并研究已知随年龄在外周免疫系统中发生的变化，这些变化可能导致与年龄相关的易受感染诱导的认知衰退影响的情况。
