Periodontitis-induced neuroinflammation triggers IFITM3-Aβ axis to cause alzheimer’s disease-like pathology and cognitive decline

作者：Lingwenyao Kong, Juanjuan Li, Lu Gao, Yonggang Zhao, Weixian Chen, Xumeng Wang, Songlin Wang, Fu Wang · 发表于：Alzheimer s Research & Therapy · 年份：2025 · DOI：10.1186/s13195-025-01818-3 · 被引用次数：18 · 研究领域：interferon and immune responses、Inflammasome and immune disorders、Oral microbiology and periodontitis research

BACKGROUND: Periodontitis is a risk factor linked to Alzheimer's disease (AD), and characterized by amyloid-beta (Aβ) pathology. Mounting evidence suggests a contributory role of periodontitis in the onset and progression of AD. Type I interferons are upregulated in Porphyromonas gingivalis (Pg)-induced periodontitis in murine models. Colonization of Pg has been identified in the brains of patients with AD. Recently, interferon-induced transmembrane protein 3 (IFITM3), an inflammation-induced innate immunity protein, was identified as a novel γ-secretase modulatory protein for Aβ production in AD. However, whether periodontitis triggers an increase in type I interferons in the brain, subsequently inducing AD-like pathology by eliciting the innate immune response of glial cells and activating the IFITM3-Aβ axis, remains unclear. Additionally, the question of whether colonization of Pg in brain induces innate immune in astrocytes and microglia remains unanswered. METHODS: We assessed the impact of Pg-induced periodontitis on cognitive impairment in C57BL/6J and APP/PS1 mice using behavioral tests. The effects of Periodontitis/Pg on microglia and astrocytes were measured using quantitative reverse transcriptase PCR (qRT-PCR), western blotting, and histological staining. RESULTS: Pg-induced periodontitis led to cognitive impairment in C57BL/6J mice and exacerbated a cognitive decline in APP/PS1 mice. Furthermore, Pg-induced periodontitis elevated the levels of interferon (IFN)-β,...