Study Rationale: To slow the progression of Parkinson disease (PD), we need to understand how, where and why the illness starts. It is estimated that most individuals with PD experience a significant reduction in their ability to smell that begins at least 20 years before the onset of motor symptoms. Using a variety of preclinical models, our team studies the PD-associated protein alpha-synuclein in nerve cell projections and circuits that extend from the nasal cavity to various regions in the brain. These studies help us to understand how genes, environmental triggers and age interact to reduce odor signaling in people with PD.
Hypothesis: We hypothesize that select environmental and genetic risk factors trigger alpha-synuclein aggregation in olfactory neurons and that this aggregation, which begins inside the relay system that processes scent perception, gradually spreads further into the brain, thereby initiating PD.
Study Design: We are defining the normal role of alpha-synuclein protein throughout the odor processing circuitry of mice and humans. We are examining whether the alpha-synuclein clumps we discovered in the nasal cavity, also called Lewy aggregates, alter individuals’ sense of smell. We have begun probing areas of the human brain that are responsible for scent processing, including by MRI scanning and in autopsy studies. Lastly, we examine nasal fluid specimens from people with PD who have been carefully tested for their sense of smell over several years to determine whether alpha-synuclein from nasal secretions could possibly serve as a PD biomarker.
Impact on Diagnosis/Treatment of Parkinson’s disease: Our study helps delineate what causes the loss of sense of smell in PD. This information could facilitate earlier diagnosis and reveal how the gradual, irreversible loss of olfaction can inform future interventions. We have already gained insights that have generated new avenues for simple, noninvasive diagnosis.
Next Steps for Development: We have already developed three methods to potentially improve PD diagnosis in the earliest stages: a simplified, easy-to-apply smell test with just eight odorants (NeuroScent Card), a new MRI protocol to map changes inside the brain and (if further validated) a nasal fluid-based test. We will now consolidate these leads.