Is there a link between genetic defects in the complement cascade and Porphyromonas gingivalis in Alzheimer’s disease?

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 complement 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 an 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 thereby contributing to formation of hallmark lesions of AD and excessive chronic inflammation.