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

The APOE4 gene, particularly the ε4 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)-α 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-α 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-α inhibition in this coexistence may have harmful effects on both the brain and kidney.