Is there a link between genetic defects in the complement cascade andPorphyromonas gingivalisin 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 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 amyloidbeta 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.

Interaction between genetic factors, Porphyromonas gingivalis and microglia to promote Alzheimer’s disease

“…It has been reported that SNPs rs3818361 and rs6656401 of the CR1 gene are associated with increased likelihood of AD [49]. This supports a CR1 gene defect in AD [5]. CR1 helps with regulating the complement cascade and promotes phagocytosis of cellular debris and Aβ plaques, and adherence of immune complexes to erythrocytes [5].…”

The Links Between the Gut Microbiome, Aging, Modern Lifestyle and Alzheimer's Disease

“…A nationwide, retrospective, matched-cohort study in Taiwan showed that patients with chronic periodontitis and gingivitis have a higher risk of developing dementia compared to those with healthy gums (Tzeng et al, 2016). Moreover, recent accumulating evidence has demonstrated a causal relationship between oral microbiome and AD (Paganini-Hill et al, 2012;Harding et al, 2017;Liu et al, 2019b;Panza et al, 2019;Olsen and Singhrao, 2020). For example, P. gingivalis, the most common periodontal bacteria causing periodontal disease, was capable of inducing accumulation of amyloidbeta plaques and neurofibrillary tangles following experimental oral infection in mice (Dominy et al, 2019).…”

Is Porphyromonas gingivalis involved in Parkinson’s disease?

“…As mentioned, proteolysis is important for this bacterium to obtain nutrition through breakdown of proteins. Gingipains are also important for degradation of antibacterial peptides [27] and for the bacterium to evade the complement system [28,29].…”