Alteration in oral and non-oral tissues in ligature-induced periodontitis mice with the Alzheimer's disease risk factor APOE4

Abstract

The APOE4 gene, particularly the epsilon 4 allele, is linked to susceptibility to Alzheimer's disease, and periodontitis can cause pathological changes in multiple organs, but combined effects of these conditions and the impact of tumor necrosis factor (TNF)-alpha regulation on the combined effects remain unclear. We examined the alterations in oral and non-oral tissues in APOE4-knockin mice with periodontitis and evaluated the effects of infliximab, a TNF-alpha inhibitor. Mice were grouped as control, periodontitis, APOE4-knockin, APOE4-knockin with periodontitis, infliximab-treated periodontitis, and infliximab-treated APOE4-knockin with periodontitis. There were no differences in alveolar bone volume and periodontal inflammatory cells among all periodontitis-induced groups. The APOE4-knockin with periodontitis group showed a decrease in hippocampal Cornu Ammonis 1 neurons (p < 0.05) and increased renal and hepatic fibrosis (p < 0.05) compared to control group. The infliximab-treated APOE4-knockin with periodontitis group had even greater neuronal loss (p < 0.001) and renal fibrosis (p < 0.01). Glial fibrillary acidic protein mRNA expression, a marker of astrocyte activation, was higher in the infliximab-treated APOE4-knockin with periodontitis group than in the control group. These suggest that APOE4 with periodontitis worsens neuronal loss and renal and hepatic fibrosis, and TNF-alpha inhibition in this coexistence may have harmful effects on both the brain and kidney.