Recent comprehensive oral-health studies demonstrate the relationship between oral pathogen, inflammation, and Alzheimer’s disease (AD). In response to oral bacterial infection, pro-inflammatory cytokines are produced by the host
[39][23]. Therefore, the increased level of cytokines lead to inflammation and may contribute to the brain inflammation that occurs among patients with Alzheimer’s disease. Moreover, dental plaque leads to periodontal diseases and changed microbiome. Periodontal pathogens such as
Porphyromonas gingivalis and
Treponema dentricola produce lipopolysaccharide (LPS). LPS constitutes a virulence factor and plays an important role in brain inflammatory process. Therefore, inflammation is a major factor responsible for neurodegeneration among patients
[40][24]. Besides LPS, also gingipains are released by
Porphyromonas gingivalis. Gingipains are classified as collagenases and trypsin-like cysteine proteinases and they are secreted by all strains of
Porphyromonas gingivalis. Gingipains together with LPS can proteolytically activate kinases such as glycogen synthase kinase-3 β (GSK-3β), which phosphorylates neuronal tau protein
[41][25]. Phosphorylated tau is an important agent, especially since the intraneuronal cytoskeletal alterations precede the formation of amyloid in patients with AD
[42][26]. Additionally, periodontal pathogens such as
Treponema dentricola and
Chlamydia pneumonia were detected in postmortem brains derived from patients with Alzheimer’s disease. Moreover,
Porphyromonas gingivalis is responsible for the peripheral and cerebral immune responses. Therefore, researchers put forward a hypothesis, that pathogens from oral cavity may invade the brain by crossing the brain–blood barrier. Periodontal pathogens may be associated with symptoms of Alzheimer’s disease
[34][18] (Figure 1).