The Smell of Parkinson’s Disease – A New Diagnostic Tool?

Following Alzheimer’s disease, Parkinson’s disease is the second most common neurodegenerative condition affecting around 6 million people worldwide. This serious illness is usually diagnosed at later stages, when most neurons have already been affected. How can the diagnosis of Parkinson’s disease be improved?

What is Parkinson’s Disease?

Parkinson’s disease is a progressive neurodegenerative disease characterised by the lack of dopamine in the central nervous system. A damaged dopaminergic system causes symptoms like tremors, rigidity (stiffness), slowed and impaired motor function, and dementia.

Motor symptoms are the basis for diagnosing Parkinson’s disease, however, they only appear when there has already been significant damage to dopaminergic neurons. Non-motor symptoms may occur up to 20 years earlier but are nonspecific. Another giveaway of Parkinson’s disease is the accumulation of protein structures called Lewy bodies, though their presence can only be confirmed post-mortem due to their location. Hence, it is crucial to find biomarkers that would enable earlier diagnosis.

A Sensitive Nose

A new direction in the search for biomarkers was uncovered by a woman named Joy Milne when she noticed a rather unusual odour on her husband. Her husband was later diagnosed with Parkinson’s disease, but she did not link the smell to the disease just yet. Later, when Joy met other patients with Parkinson’s disease, she noticed the same unusual odour and so uncovered her gift.

When she explained to researchers that she could smell Parkinson’s disease, they were sceptical. However, a blind experiment showed that she could indeed accurately determine which item of clothing belonged to people suffering from the disease, and which belonged to healthy individuals. She made one “mistake” when she identified a man from the control group as positive for having Parkinson’s disease. However, that same man was later diagnosed with Parkinson’s disease.

Biomarkers in Sebum

Mrs Milne’s ability to distinguish people with the disease purely by the smell of their clothes inspired scientists to further investigate what exactly is causing the odour. It has been concluded that the smell comes from areas of the body with high sebum production. Sebum is a waxy substance secreted by sebaceous glands. Moreover, excessive sebum production is also a symptom of Parkinson’s disease.

Researchers focused on volatile organic compounds that are often responsible for various distinctive smells. Elevated levels of lipid-based compounds such as hippuric acid, eicosane, perillaldehyde, and octadecanal stood out among the results. Several hypotheses were then proposed to explain the retention of these compounds.

One theory suggests that these lipophilic substances are retained in greater amounts when ingested due to increased sebum secretion. Another possibility is that more lipid molecules needed for bacterial growth are being produced on the skin due to the changed microbiome of Parkinson’s patients.

The Future of Treatment

Despite the initial research showing promising results, these findings only serve as the base for further studies. Molecules that will completely differentiate the sebum of people with and without the disease are still being explored as potential non-invasive biomarkers for early Parkinson’s disease diagnosis when motor symptoms have not developed yet.

Even though the link between these biomarkers and Parkinson’s disease itself still needs to be fully confirmed, the sebum analysis is a promising pathway in finding new diagnostic progress. Naturally, early diagnosis enables early treatment, which could significantly improve patient outcomes.