Porphyromonas gingivalis is a Strong Risk Factor for Alzheimer’s Disease

Abstract

Porphyromonas gingivalis (P. gingivalis) is one of the several important bacterial pathogens associated with the sporadic Alzheimer’s disease (AD). Different serotypes are either capsulated or are non-capsulated. It has been demonstrated that P. gingivalis (non-capsulated) can reproduce the neurodegenerative AD-like changes in vitro, and a capsular P. gingivalis (strain W83) could reproduce the cardinal hallmark lesions of AD in a wild-type mouse model. All P. gingivalis forms express proteolytically active proteases that enable cleavage of the amyloid-β protin precursor (AβPP) and tau resulting in the formation of amyloid-β and neurofibrillary tangles. Tau is an established substrate for gingipains, which can cleave tau into various peptides. Some of the P. gingivalis fragmented tau protein peptides contain “VQIINK” and “VQIVYK” hexapeptide motifs which map to the flanking regions of the microtubule binding domains and are also found in paired helical filaments that form NFTs. P. gingivalis can induce peripheral inflammation in periodontitis and can also initiate signaling pathways that activate kinases, which in turn, phosphorylate neuronal tau. Periodontal disease related inflammation has metabolic implications for an individual’s peripheral and brain health as patients suffering from generalized periodontitis often have related co-morbidities and are “at risk” of developing AD. The aim here is to discuss the role of P. gingivalis behind such associations with the backdrop of huge efforts to test P. gingivalis virulence factors clinically (GAIN Trial: Phase 2/3 Study of COR388 in Subjects with AD) with inhibitors, which may lead to an intervention by reducing the pathogenic bacterial load.

Alzheimer's Disease and Oral-Systemic Health: Bidirectional Care Integration Improving Outcomes

“…There is increasing evidence implicating the polymicrobial infection with P. gingivalis as playing a part in disease pathogenesis, not only from the low-grade inflammation but the actual translocation into the brain vasculature [64]. A link between Alzheimer's and P. gingivalis in the brain is consistent with this emerging model for microbes in the disease's etiology [58,[73][74][75].…”

Utilizing Red Spotted Apollo Butterfly Transcriptome to Identify Antimicrobial Peptide Candidates against Porphyromonas gingivalis

“…Fifteen peptides were tested against several bacterial and fungal strains, but only three peptides showed antibacterial and antifungal activity. P. gingivalis is a human pathogenic bacteria causing periodontitis [ 32 , 33 ], and its noted association with other disease like Alzheimer’s disease [ 34 , 35 ] is a serious threat to human health. Identifying novel drug candidates against P. gingivalis will add value to a treatment regimen.…”

Can Porphyromonas gingivalis Contribute to Alzheimer’s Disease Already at the Stage of Gingivitis?

“…A number of studies have reported an association between periodontitis and AD [19][20][21][22][23][24][25][26][27][28]. Several reports have suggested how virulence factors of P. gingivalis can contribute to AD, particularly LPS, gingipains, PPAD (P. gingivalis peptidylarginine deiminase), Mfa1 fimbrial protein, BCAT (branched-chain amino acid aminotransferase), and capsular polysaccharides [29][30][31][32][33][34].…”