BackgroundThe existence of an interconnected mechanism between cognitive disorders and periodontitis has been confirmed by mounting evidence. However, the role of age or sex differences in this mechanism has been less studied. This study aims to investigate sex and age differences in the characterization of periodontal bone tissue, immune state and cognitive function in amyloid precursor protein/presenilin 1(APP/PS1) murine model of Alzheimer’s disease (AD).MethodsThree- and twelve-month-old male and female APP/PS1 transgenic mice and wild-type (WT) littermates were used in this study. The Morris water maze (MWM) was used to assess cognitive function. The bone microarchitecture of the posterior maxillary alveolar bone was evaluated by microcomputed tomography (micro-CT). Pathological changes in periodontal bone tissue were observed by histological chemistry. The proportions of helper T cells1 (Th1), Th2, Th17 and regulatory T cells (Tregs) in the peripheral blood mononuclear cells (PBMCs) and brain samples were assessed by flow cytometry.ResultsThe learning ability and spatial memory of 12-month-old APP/PS1 mice was severely damaged. The changes in cognitive function were only correlated with age and genotype, regardless of sex. The 12-month-old APP/PS1 female mice exhibited markedly periodontal bone degeneration, evidenced by the decreased bone volume/total volume (BV/TV), trabecular thickness (Tb.Th), and bone mineral density (BMD), and the increased trabecular separation (Tb.Sp). The altered periodontal bone microarchitecture was associated with genotype, age and females. The flow cytometry data showed the increased Th1 and Th17 cells and the decreased Th2 cells in the brain and PBMC samples of 12-month-old APP/PS1 mice, compared to age- and sex-matched WT mice. However, there was no statistical correlation between age or sex and this immune state.ConclusionsOur data emphasize that age and sex are important variables to consider in evaluating periodontal bone tissue of APP/PS1 mice, and the cognitive impairment is more related to age. In addition, immune dysregulation (Th1, Th2, and Th17 cells) was found in the brain tissue and PBMCs of APP/PS1 mice, but this alteration of immune state was not statistically correlated with sex or age.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12974-023-02790-1.