The aggregation of beta-amyloid (Aβ) into plaques in the extracellular compartment of the brain is a pathological
hallmark of Alzheimer’ s disease (AD). Although the pathways for misprocessing of Aβ leading to plaque formation
are not well understood, they may be related to synapse turnover and neuron activity. In this study, we have utilised transgenic
mice co-expressing mutations in the amyloid precursor protein and presenilin 1 genes (APP/PS1) to determine how
long-term denervation of the olfactory bulb, a CNS area affected early by AD-like pathology, may affect Aβ plaque formation.
The olfactory bulb of pre-symptomatic mice was denervated by ablating the olfactory epithelium unilaterally with
Triton X-100 solution. Mice were subjected to nasal washes for a total of 4 or 8 times, at 3-week intervals either with 1%
Triton X-100 solution or phosphate buffered saline (sham denervation). Denervation of the olfactory bulb resulted in a
statistically significant (p<0.05) decrease in amyloid plaque load in the ipsilateral olfactory bulb, and bilaterally also in the
neocortex and hippocampus at 8-9 months age. Amyloid precursor protein was predominantly expressed by mitral cells in
the olfactory bulb, which are normally postsynaptic to olfactory axons. The number of APP positive mitral cells was significantly
increased in the denervated olfactory bulb of wild type but not of the APP/PS1 mice, which consistently showed
high immunoreactivity for APP pre- and post-denervation. In summary, our results show that Aβ plaque deposition in the
central nervous system can be modified transsynaptically by deafferentation.
Keywords: Alzheimer’ s disease, amyloid plaque load, amyloid precursor protein, denervation, olfactory bulb.
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