ABSTRACT

Defects, as determined by Genome-Wide Association Studies (GWAS), in the complement cascade of innate immunity have been suggested to play a key role in Alzheimer’s disease (AD). These defective genes encode sub-component 1s (C1s), complement receptor 1, complement component 9, and clusterin, a fluid-phase regulatory protein. A dysregulated complement cascade has been shown to relate to cell activation, defective complement mediated clearance and possible cognitive decline in AD patients. Porphyromonas gingivalis, a putative keystone pathogen of periodontal disease, has been reported to be associated with human AD. The inflammatory burden following experimental oral infection in mice and putative entry of this bacterium into the brain appears to drive the formation of amyloid-beta plaques and neurofibrillary tangles with loss of cognition. P. gingivalis is a master of immune subversion in this inflammatory cascade and may establish microbial dysbiosis where it is located. Here we discuss if P. gingivalis may enhance the detrimental effects of the defective GWAS complement cascade protein genes.

摘要

由基因组广泛关联研究（GWAS）确定的先天免疫的补体级联中的缺陷已被证明在阿尔茨海默氏病（AD）中起关键作用。这些缺陷基因编码亚成分1s（C1s），补体受体1，补体成分9和簇蛋白（一种液相调节蛋白）。已经显示失调的补体级联与AD患者的细胞活化，补体介导的缺陷清除和可能的认知下降有关。牙龈卟啉单胞菌据报道，牙周病的一种可能的关键性病原体是人AD。小鼠经实验性口腔感染后的炎性负担以及该细菌推定进入脑后，似乎会导致淀粉样β斑块和神经原纤维缠结的形成，并丧失认知能力。牙龈卟啉单胞菌是该炎性级联反应中免疫颠覆的大师，并且可能在其所处的地方建立微生物营养不良。在这里，我们讨论牙龈卟啉单胞菌是否可以增强有缺陷的GWAS补体级联蛋白基因的有害作用。