Table 1: Relevant data gathered from the selected studies on mice.

Authors (Years)	Country	Via of P. gingivalis contamination	Sample size	Part tested	Technique used for evaluation	Result	Conclusion
Dominiy S, et al. [13]	USA	Experimental periodontitis was induced by ligature placement.	40 43- to 44-week- old female or 100 8 week old female	Brain tissue (hippocampus)	ELISA PCR	• Higher number of degenerating neurons were found in mice inoculated with gingipain than mice injected with saline. • Oral P. gingivalis infection in mice lead to brain colonization and higher production of Ab_1-42. • Gingipains are neurotoxic in vivo and in vitro, providing detrimental effects on protein tau, needed for normal neuronal function.	• P. gingivalis and gingipains in the brain have a primordial role in the pathogenesis of Alzheimer's disease. • P. gingivalis DNA and gingipain antibodies were found in AD brains. • Small-molecule gingipain inhibitors administrable orally blocks neurodegeneration induced by gingipains, lead to P. gingivalis level in mice brain, and significantly decreases the host Ab_1-42 response to P. gingivalis brain infection.
Kenyu H, et al. [14]	Japan	Intracerebroventricular (ICV) injection of PgLPS	19 mice: 6 young and 13 middle age	Entire brain (injection ICV)	Y. Morris water-maze and maze test Immuno-histochemical	• Acute and continuous brain exposure of Pg-LPS didn't lead to positive findings on AD model. • Mice with vehicle or PgLPS did not show significant difference of Y-maze and Morris water maze tests. • Pg-LPS induced cardiac atrophy in both young and middle-aged mice.	• Continuous brain exposure of Pg-LPS initiated sarcopenias and cardiac injury without intensify cognitive impairment in Alzheimer's disease model mice. • Continuous brain exposure pf P-LPS is not deleterious in healthy individual but can deteriorate prognosis od AD patients. • Acute brain exposure of pg-LPS has little positive effect in AD patients.
Ye Ding, et al. [17]	China	Oral inoculation of P. gingivalis using feeding needles (0.1 ml of P. gingivalis in 2% carboxymethyl cellulose	60 mice's: 30 aged of 4 week and 30 twelve month old	Behavior brain tissues (cerebral cortex)	Morris water maze qRTPCR ELISA Immuno-histochemistry	• Learning and memory abilities of the middle-aged P. gingivalis infected mice were decreased. • Laud of the pro-inflammatory cytokines TNF-α, IL-6 and IL-1β in the brain tissues of middle-aged mice P. gingivalis infected mice were higher.	P. gingivalis periodontal infection could lead to cognitive impairment via the increase of the proinflammatory cytokines TNF-α, IL-6 and IL-1β in cerebral tissues of middle-aged mice.
Ran Nie, et al. [18]	China	Injection of P. gingivalis intraperitoneally	Females mice aged of 12 months	Liver	PCR Immuno-fluorescence western blotting	• Chronic systemic P. gingivalis infection induces a quantity independent increase in TLR2 and IL-1β levels in liver macrophages of middle-aged mice. • Chronic systemic P. gingivalis infection increases the Aβ PP, CatB and Ab production in liver macrophages of middle-aged mice.	• Chronic systemic P. gingivalis infection caused the Aβ deposit in inflammatory monocytes/macrophages via the stimulation of CatB/NF-κB signaling, implying that monocytes/macrophages serve as mean of transport of Aβ in patients with periodontitis. • CatB might be a n new therapeutic target for preventing the periodontitis-related Alzheimer disease onset and development.
Vladimir Ilievski, et al. [16]	USA	μl of Pg in CMC containing 109 Pg was applied (2 applications of 50 μl 3x/week) in the oral cavity	Mice aged of 8 weeks	Hippocampus	Immuno-fluorescence microscopy Confocal microscopy Quantitative PCR	• Pg/gingipains was detected in the hippocampi of mice in the experimental group, localized intranuclearly, peri-nuclearly and extracellularly. • Significant higher level of IL6, TNF-α and IL1β in the experimental group. • Greater number of degenerations of neuron in the experimental group • Phosphorylated Tau protein was detected in experimental group.	• After several P. gingivalis oral infection, neurodegeneration and formation of extracellular Aβ₄₂ was found. • Chronic oral infection of Pg can be an initiator of the development of Alzheimer's disease.
Naoyuki Ishida, et al. [3]	Japan	Experimental periodontitis by inoculation of P. gingivalis mixed with carboxymethyl cellulose, which was delivered orally	Transgenic mice model	Behavior brain tissues (hippocampus, cortex)	The novel objection test ELISA	• Cognitive function was significantly impaired in periodontitis-induced mice. • Levels of Aβ, Aβ40, and Aβ42 accumulation in the hippocampus and cortex were increased in P. gingivalis infected APP-Tg mice. • Brain levels of IL-1β and TNF-α were increased in infected mice. • LPS Level were higher in serum and brain of P. gingivalis-infected mice. • P. gingivalis LPS lead to production Aβ in neural cell cultures and augmentation of TNF-α and IL-1β production in a culture of microglial cells primed with Aβ.	Periodontitis induced by P. gingivalis may intensify brain Aβ accumulation, causing cognitive impairments, by a mechanism that engage neuroinflammation.
Zhou Wu, et al. [1]	Japan	Systemic exposure to PgLPSl daily (1 mg/kg/day, intraperitoneally; for 5 week	18 mice: 6 adults, 6 middle-aged and 6 Cat-/-	Hippocampus	Passive avoidance test locomotor activity RT-PCR Immuno- blotting Immuno- fluorescence ELISA	Chronic systemic exposure to PgLPS: • Leads to CatB-dependent learning and memory impairments mice of middle-age. • Induces CatB production in neuron and microglia in the middle-aged mice. • Increases CatB-dependent IL-1β synthesis in microglia in mice of middle-age CatB-dependent TLR2 and TLR4 are increased in microglia in the middle-aged mice. • Induces CatB-dependent Aβ deposition in neurons in mice of middle-age.	• Chronic systemic exposure to PgLPS lead to Alzheimer's disease -like features, as learning and memory impairment, microglia mediated neuroinflammation and A-β deposition, in mice of middle-age • These observations strongly imply that CatB plays a primordial role in the link • Between periodontitis and Alzheimer's disease. CatB may be use as therapeutic tool for preventing periodontitis associated cognitive decline in Alzheimer's disease.
Poole, et al. [25]	UK	oral infection of ApoE-/- mice with periodontal pathogens for a chronic infection period of 24 week	12 mices	Brain tissues (hippocampus, dentate gyrus, lateral ventricle)	PCR Immuno- blotting	• Oral infection to P. gingivalis in ApoE-/- mice was able to enter the brain. • At 12 weeks, 6 out of 12 ApoE-/- mice brains presented P. gingivalis DNA.	• Complement cascade, activated in response to P. gingivalis brain infection supports the hypothesis that chronic local inflammation plays a role in development of Alzheimer's disease. • P. gingivalis in the brain induced damage complement mediated in absence of Aβ deposition.