Association of P. gingivalis with Cognitive Impairment among Elderly Pakistani Population and its Effects on Conformational Changes in Amyloid-β Proteoforms

Abstract

Oral hygiene parameters may have a significant impact on cognitive abilities, and the invasion of the P. gingivalis pathogen is involved in periodontitis which potentially leads to dementia in the elderly Pakistani population. It was found that 75% of the total samples validated the presence of P. gingivalis and had a cognitive impairment observed through MMSE scores with a range of 0– 17 in the elderly population of Pakistan. The computational study indicated that the amyloid-β proteoforms involved in rapidly progressive Alzheimer’s disease interact more closely with the gingipain proteins of P. gingivalis than proteoforms involved in sporadic Alzheimer’s disease. The proteoforms Aβ1-12, Aβ1-40, Aβ1-42, Aβ2-14, Aβ3-14, Aβ3-42, Aβ4-40, Aβ4-42, Aβ5-27, Aβ9-40, Aβ11-42, and Aβ15-38 computationally interacted with Kgp and RgpB had a significantly higher binding score with Kgp when docked via Hex 8.0. Aβ1-42 interacting with Kgp had the highest binding score of -905.31 kJ/mol among all other proteoforms. These interactions potentially lead to structural modification in the Aβ protein, causing plaque formation and aggregation, potentially leading to cognitive impairment. The common residues involved in Aβ1-42 interaction with Kgp and RgpB are GLY37, GLU11, HIS13, LYS16, ALA21, PHE19, VAL18, GLU22, GLY33, LEU34, ILE31, VAL39, SER26, LYS28, GLY29, and ASN27. These residues were most commonly found in the pathological pathways, cell signaling, and maintenance of protein structure and stability.