Periodontitis, especially in its chronic form, is one of the leading causes of tooth loss, significantly affecting the quality of life in the modern era of aging society. Recent studies have revealed a potential correlation between periodontitis and various systemic diseases, including cardiovascular diseases and Alzheimer’s dementia (AD). With the body of epidemiologic evidence that links these separate disease entities, several lines of hypotheses have been postulated to provide mechanistic understandings that mostly comprises abnormal regulation of immunologic and inflammatory signaling. In this review, we revisit the experimental findings that describe virulence factors derived from Porphyromonas gingivalis, including gingipains and lipopolysaccharides, as well as their roles in the pathophysiology of AD. In addition, we address potential immunologic challenges imposed by this bacterial pathogen contributing to progression of AD.

Abstract
Ⅰ. INTRODUCTION
Ⅱ. P. gingivalis-induced gingipain as asignificant molecular player to accelerateAlzheimer’s dementia
    1. Gingipain as an important exotoxin derivedfrom P. gingivalis
    2. Host system damage induced by gingipains
    3. Gingipain as a contributing factor toAlzheimer’s dementia
Ⅲ. Expression of pathophysiologic hallmarksof Alzheimer’s dementia influenced bygingipains
    1. The β-amyloid plaques as a representativepathophysiologic hallmark of Alzheimer’sdementia
    2. Accumulation of the β-amyloid plaquesfacilitated by gingipains
    3. Neurofibrillary tangles and its formationinfluenced by gingipains
    4. Clinical trials of gingipain inhibitors to treatAlzheimer’s dementia
Ⅳ. Lipopolysaccharide as a significant riskfactor to accelerate Alzheimer’s dementia
    1. Lipopolysaccharide as an importantendotoxin derived from P. gingivalis
    2. Cellular mechanisms underlyinglipopolysaccharide-induced microglialdamage linked to Alzheimer’s disease
    3. A novel hypothesis of LPS-induced myelindamage as a potential link betweenP. gingivalis-derived lipopolysaccharide andAlzheimer’s dementia
Ⅴ. A relationship between immune evasion ofP. gingivalis and Alzheimer’s dementia
    1. Immune evasion of infectious pathogensfrom the host innate immunity
    2. Complement system as a target of immuneevasion by bacterial pathogens
    3. Immune evasion mechanisms of P. gingivalis
    4. Evasion of innate immunity by P. gingivalisand Alzheimer’s dementia
Ⅵ. Conclusion
ACKNOWLEDGMENTS
REFERENCES

• 부가영(부산대학교 치과대학 치의학과) | Ka Young Boo (Department of Dentistry)
• 최대솔(부산대학교 치과대학 치의학과) | Dae Sol Choi (Department of Dentistry)
• 곽혜원(부산대학교 치과대학 치의학과) | Hye Won Gwak (Department of Dentistry)
• 전다은(부산대학교 치과대학 치의학과) | Da Eun Jeon (Department of Dentistry)
• 강수은(부산대학교 치과대학 치의학과) | Su Eun Kang (Department of Dentistry)
• 이민서(부산대학교 치과대학 치의학과) | Min Seo Lee (Department of Dentistry)
• 박태영(부산대학교 치과대학 치의학과) | Tae Young Park (Department of Dentistry)
• 심현룡(부산대학교 치과대학 치의학과) | Hyeon Ryong Shim (Department of Dentistry)
• 이지혜(부산대학교 치과대학 치의학과, 구강병리학교실, 치주질환 신호네트워크 연구센터, 치의생명과학연구소) | Ji Hye Lee (Department of Dentistry, Department of Oral Pathology, Periodontal disease signaling network research center, School of Dentistry, Dental and Life Science Institute, Pusan National University) Corresponding author