Trigeminal Neurodegeneration Affects Masticatory Function in Alzheimer Model Mice

Objectives: The oral health condition has been reported to be involved in the progression of Alzheimer's disease (AD). However, it is unclear whether neurodegeneration affects masticatory function in AD. The purpose of this study is to clarify the neurodegeneration in trigeminal nervous system in elder AD model mice and the effects of the trigeminal neurogeneration in masticatory function.
Methods: We analyzed 6-month-old triple transgenic (3xTg-AD) mice harboring APP_SWE, PS1_M146V, and tau_P301L transgenes, and C57BL/6 wild type (WT) mice as control. We immunohistochemically examined the distribution of amyloid beta, transgene related tau, and phosphorylated tau (Ser396) at the trigeminal ganglion and trigeminal nuclei in 3xTg-AD and C57BL/6 mice. Further, masticatory function was assessed by electromyogram (EMG) of masseter muscles.
Results: Both types of mice showed phosphorylated tau distribution in the trigeminal nerve fiber, while neither amyloid beta nor transgene related tau was found in the soma of trigeminal neurons in the trigeminal ganglion, principal sensory trigeminal nucleus, and spinal trigeminal nucleus. Characteristically in 3xTg-AD mice, the deposition of amyloid beta and transgene related tau was found in mesencephalic trigeminal nucleus (MesV) and motor trigeminal nucleus (MoV). Strong phosphorylated tau expression was found in the nerve fiber between MesV and MoV in 3xTg-AD mice. Morphologically, 3xTg-AD mice had less attrition of molar than WT mice. EMG analysis of masseter muscles revealed that the frequency of mastication was significantly reduced in 3xTg-AD mice (70% vs. control, p < 0.001), which means 3xTg-AD mice have slower chewing pattern.
Conclusions: These findings indicate that neuropathological change between MesV and MoV in AD model mice would result in the reduction in masticatory function.