Trigeminal Mesencephalic Neurodegeneration in Alzheimer’s Disease Decreases Masticatory Function

Objectives: Oral deterioration (i.e., oral frailty) is closely related to aging. Recent studies reported that Alzheimer’s disease (AD) patients showed oral frailty. However, the causal relationship between oral frailty and cognitive dysfunction is unknown. Therefore, we aimed to evaluate the masticatory function in a triple transgenic mouse model of AD (3×Tg-AD) and investigate the pathological mechanism of oral frailty.
Methods: We developed a system to simultaneously measure electromyography of the masseter muscle and bite force in mice. Using this system, the bite force of 12–16-week-old 3×Tg-AD male mice corresponding to the stage of mild cognitive impairment was measured. As a control, C57BL/6J mice with homologous genetic background were used. Moreover, we immunohistochemically analyzed the pathogenesis of AD in the trigeminal nuclei, which is important for mastication.
Results: Electromyography in the masseter during feeding revealed a significant delay in mastication rhythm in 3×Tg-AD mice compared with C57BL/6J mice. Because muscle activity in electromyogram analysis of the masseter showed a high correlation with bite force and energy, the bite force and energy could be accurately estimated from muscle activity. The estimated bite force and energy of 3×Tg-AD mice while eating sunflower seeds were smaller than the estimated bite force and energy of C57BL/6J mice. The maximum bite force was decreased in 3xTg-AD mice. However, there was no significant difference in the weight of the masseter or the cross-sectional area of the muscle fibers, suggesting that the decreased bite force and delayed mastication rhythm observed in 3×Tg-AD mice were not due to sarcopenia. Immunohistochemical analysis showed amyloid β deposition and excessive tau phosphorylation in the mesencephalic trigeminal nucleus (Vmes), which is important for the control of mastication, in 12-week-old 3×Tg-AD mice.
Conclusions: Decreased masticatory function observed in 3xTg-AD mice would be caused by neurodegeneration in the Vmes.