Intracerebral but Not Peripheral Infection of Live Porphyromonas gingivalis Exacerbates Alzheimer's Disease Like Amyloid Pathology in APP-TgCRND8 Mice

• Published in: International journal of molecular sciences Vol. 23; no. 6; p. 3328
• Main Authors: Aravindraja, Chairmandurai, Sakthivel, Ravi, Liu, Xuefei, Goodwin, Marshall, Veena, Patnam, Godovikova, Valentina, Fenno, J Christopher, Levites, Yona, Golde, Todd E, Kesavalu, Lakshmyya
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 19.03.2022; MDPI
• Subjects: Alveolar bone; Alzheimer Disease - metabolism; Alzheimer's disease; Amyloid; Amyloid beta-Peptides - metabolism; Amyloid beta-Protein Precursor - genetics; Amyloid beta-Protein Precursor - metabolism; amyloid β plaques; Amyloidosis; Animals; APP-TgCRND8 mouse model; Bacteria; Bacterial infections; Bone resorption; Brain; Chronic infection; Dementia; Deposition; Disease Models, Animal; Dysbacteriosis; Glial fibrillary acidic protein; Gliosis; Gliosis - pathology; Gum disease; Immune response; Immunoglobulin G; Infections; Inoculation; intracerebral infection; Medical research; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microorganisms; Neuropathology; Oral infection; Pathology; periodontitis; Plaque, Amyloid - metabolism; Porphyromonas gingivalis; Porphyromonas gingivalis - metabolism; Rodents; Streptococcus infections; Transgenic mice; gliosis; APP-TgCRND8 mouse model; Alzheimer’s disease; amyloid β plaques; intracerebral infection; periodontitis
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23063328

The impact of oral microbial dysbiosis on Alzheimer's disease (AD) remains controversial. Building off recent studies reporting that various microbes might directly seed or promote amyloid β (Aβ) deposition, we evaluated the effects of periodontal bacteria ( and supragingival commensal ( ) oral bacterial infection in the APP-transgenic CRND8 (Tg) mice model of AD. We tracked bacterial colonization and dissemination, and monitored effects on gliosis and amyloid deposition. Chronic oral infection did not accelerate Aβ deposition in Tg mice but did induce alveolar bone resorption, IgG immune response, and an intracerebral astrogliosis (GFAP: glial fibrillary acidic protein). In contrast, intracerebral inoculation of live but not heat-killed increased Aβ deposition and Iba-1 (ionized calcium-binding adaptor-1) microgliosis after 8 weeks of bacterial infection but not at 4 days. These data show that there may be differential effects of infectious microbes on glial activation and amyloid deposition depending on the species and route of inoculation, and thereby provide an important framework for future studies. Indeed, these studies demonstrate marked effects on amyloid β deposition only in a fairly non-physiologic setting where live bacteria is injected directly into the brain.