Grant: CIHR Fellowship

Olfactory dysfunction is an early symptom of Parkinson's disease (PD), and other neurodegenerative diseases, and is of high interest to improve early diagnosis of disease. The olfactory bulb is the first brain region involved in olfactory processing and it was shown to be the first area that is involved in Parkinson's disease pathology. Clinical diagnostic accuracy for Parkinson's disease is low, about 70%, and the most misdiagnosed condition is Progressive Supranuclear Palsy, a condition that is clinically similar but that presents with a different underlying pathology in the brain and therefore does not answer well to the same treatments. Moreover, Alzheimer's disease pathology was shown to co-occur with Parkinson's disease in 30% of cases which can also affect clinical presentation and answer to therapeutic agents. The confirmation of these diseases is made after death with neuropathological investigations. To better understand the alterations in Parkinson's disease, we aim to assess the pathology of the olfactory bulb in patients that had died with both a clinical diagnosis and a pathological validation of Parkinson's disease in comparison to Progressive supranuclear Palsy, Alzheimer's disease and individuals without any neurodegenerative diseases. We will use histopathologic techniques to identify the type of cells that are first affected in the disease, and we will use molecular techniques to identify the differentially expressed genes between groups. We will correlate these findings with clinical severity of the disease and clinical measures of olfaction. This study will help to underline the affected mechanisms in Parkinson's disease specifically when compared to other neurodegenerative diseases. This may lead to the discovery of new targets for disease-modifying treatments, and refinements of olfactory testing that may lead to increased precision of clinical diagnoses.