Reduced Autophagy in Aged Trigeminal Neurons Causes Amyloid β Diffusion

Area of Science:

• Neuroscience
• Cell Biology
• Gerontology

Background:

• The link between oral health and Alzheimer's disease (AD) in the elderly remains unclear.
• The role of trigeminal nervous system aging and neurodegeneration in AD pathogenesis, specifically amyloid-beta (Aβ) oligomer accumulation, is unknown.
• Selective autophagy's function in the trigeminal mesencephalic nucleus (Vmes) concerning Aβ oligomer diffusion requires investigation.

Purpose of the Study:

• To examine selective autophagy and Aβ oligomer processing in aging Vmes neurons.
• To determine if Vmes neuron degeneration influences Aβ oligomer diffusion.
• To elucidate the role of autophagy in maintaining Vmes neuron homeostasis and its relation to AD development.

Main Methods:

• Utilized female transgenic 3xTg-AD and App knock-in mice (2-8 months old).
• Conducted immunohistochemical analysis of aging-related changes in selective autophagy and Aβ processing within the Vmes.
• Induced Vmes neuron degeneration via maxillary molar extraction to assess Aβ oligomer kinetics.

Main Results:

• Autophagosome-like membranes positive for Aβ, HO-1, and LC3B were found in Vmes neurons of 3xTg-AD mice.
• Extracellular Aβ42 oligomers and clusters were prominent in App mice, with increased diffusion linked to Rubicon expression (indicating autophagy deterioration) and Vmes neuron aging.
• Tooth extraction elevated extracellular Aβ42 oligomer levels in App mice.

Conclusions:

• Autophagy is crucial for maintaining homeostasis in Vmes neurons.
• Aging or neurodegeneration-induced autophagy impairment promotes Aβ42 oligomer diffusion into the extracellular space.
• This diffusion may contribute to the pathogenesis of Alzheimer's disease.