title: Denervation of the olfactory bulb leads to decreased Aβ plaque load in a transgenic mouse model of Alzheimer' s disease.
abstract: 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.
authors.affiliation: Wicking Dementia Research and Education Centre, University of Tasmania, Hobart, Tasmania, Australia.
authors.forename: Oiivier
authors.initials: O
authors.lastname: Bibari
authors.forename: Siak
authors.initials: S
authors.lastname: Lee
authors.forename: Tracey C
authors.initials: TC
authors.lastname: Dickson
authors.forename: Stan
authors.initials: S
authors.lastname: Mitew
authors.forename: James C
authors.initials: JC
authors.lastname: Vickers
authors.forename: Meng I
authors.initials: MI
authors.lastname: Chuah
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D017763:Autonomic Denervation / Q000379:methods*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009830:Olfactory Bulb / Q000378:metabolism* / Q000473:pathology; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology; D053764:Presenilin-1 / Q000235:genetics
chemical_list: D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; D053764:Presenilin-1