Abnormal amyloid precursor protein processing in periodontal tissue in a murine model of periodontitis induced by Porphyromonas gingivalis

• DOI: 10.1111/jre.13224
• Publication Date: 2024-02-05T03:39:11Z
• Authors: Hui Shen; Yiting Jiang; Che Qiu; Xinyi Xie; Huanyu Zhang; Zhiyan He; Zhongchen Song; Wei Zhou
• Keywords: 0303 health sciences; Amyloid beta-Peptides; Tumor Necrosis Factor-alpha; Interleukin-6; Interleukin-8; Alveolar Bone Loss; X-Ray Microtomography; DNA; Mice; Amyloid beta-Protein Precursor; Disease Models, Animal; 03 medical and health sciences; Animals; Aspartic Acid Endopeptidases; RNA, Messenger; Amyloid Precursor Protein Secretases; Periodontitis; Porphyromonas gingivalis

AbstractObjectiveThe study aimed to investigate the change of amyloid precursor protein (APP) processing and amyloid β (Aβ) metabolites in linking periodontitis to Alzheimer's disease (AD).BackgroundAβ is one of the main pathological features of AD, and few studies have discussed changes in its expression in peripheral tissues or analyzed the relationship between the peripheral imbalance of Aβ production and clearance.MethodsA murine model of periodontitis was established by oral infection with Porphyromonas gingivalis (P. gingivalis). Micro‐computed tomography (Micro‐CT) was used to observe the destruction of the alveolar bone. Nested quantitative polymerase chain reaction (qPCR) was used to measure small quantities of P.gingivalis DNA in different tissues. Behavioral experiments were performed to measure cognitive function in the mice. The mRNA levels of TNF‐α, IL‐6, IL‐8, RANKL, OPG, APP695, APP751, APP770, and BACE1 in the gingival tissues or cortex were detected by RT‐PCR. The levels of Aβ1‐40 and Aβ1‐42 in gingival crevicular fluid (GCF) and plasma were tested by ELISA.ResultsP. gingivalis oral infection was found to cause alveolar bone resorption and impaired learning and memory. P.gingivalis DNA was detected in the gingiva, blood and cortex of the P.gingivalis group by nested qPCR (p < .05). The mRNA expression of TNF‐α, IL‐6, IL‐8, RANKL/OPG, and BACE1 in the gingival tissue was significantly higher than that in the control group (p < .05). Similarly, upregulated mRNA levels of APP695 and APP770 were observed in the gingival tissuses and cortex of the P. gingivalis group (p < .05). The levels of Aβ1‐40 and Aβ1‐42 in the GCF and plasma of the P. gingivalis group were significantly higher than those in the control group (p < .05).ConclusionP. gingivalis can directly invade the brain via hematogenous infection. The invasion of P. gingivalis could trigger an immune response and lead to an imbalance between Aβ production and clearance in peripheral tissues, which may trigger an abnormal Aβ metabolite in the brain, resulting in the occurrence and development of AD.