Olfactory system pathology as a model of Lewy neurodegenerative disease

Olfactory dysfunction has gained recognition as an early and nearly universal feature of Lewy body Parkinson's disease (PD). Recently, research efforts have focused on the use of early non-motor symptoms of PD as early biomarkers and have suggested that investigating neurodegeneration in the aspects of the nervous system subserving these symptoms may offer important insights into the pathophysiology of Lewy body PD. Therefore, there has been interest in characterizing the pathology observed in the olfactory bulb and system of patients with PD, dementia with Lewy bodies and perhaps more importantly, in subjects with incidental Lewy pathology, defined as people with Lewy pathology without evidence of Parkinsonism or dementia during life. The olfactory bulb may be ideally suited to investigations into the pathophysiology of the Lewy body disorders as it is one of the few areas of the brain wherein the entirety of neurons susceptible to Lewy neurodegeneration, including the dendritic arborization, cell soma, axon and synaptic terminals, can be examined in the same preparation. Interestingly, there is a lack of Lewy neurodegeneration in the dopaminergic neurons of the olfactory bulb and paradoxically, an apparent increase in dopaminergic neurons in some PD patients compared to controls. In this report, the known neuropathology of the olfactory system in PD will be reviewed and the advantages of investigating degeneration of the olfactory bulb as a model of Lewy neurodegeneration will be discussed.