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Can you smell Parkinson's ?


Parkinson's disease is the second most common age-related neurodegenerative disease with a prevalence of approximately 2% in people over the age of 65. It is currently predicted that over 20 million people worldwide will suffer from the disease by 2050. Therefore, intensive research is being conducted to develop new therapies and biomarkers that indicate the disease before the onset of symptoms. Interestingly, recent findings suggest that Parkinson's-associated metabolites are also present in sebum on the skin and can be detected using chemical methods.


Ten years ago, neuroscientist Tilo Kunath met Joy Milne, a Scottish woman, at an event organized by Parkinson's United Kingdom, a research and support organization in England. She made headlines because of her ability to recognize Parkinson's patients by their body odor. The retired nurse suffers from hereditary hyperosmia, a hypersensitivity to smells. She noticed early on that her husband smelled of musk (a scent she had not previously detected on him). Then, when he was diagnosed with Parkinson's many years later, she linked the change in smell to the disease.


Dr. Kunath tested Joy Milne's abilities on twelve T-shirts (six from people with Parkinson's and six from healthy individuals). Surprisingly, she correctly identified the disease in all six cases, although it initially appeared that she was wrong about one person (but that person was also diagnosed with Parkinson's within a year). High-intensity research was then conducted on a Parkinson's-specific substance in order to be able to develop a simple test based on a skin swab that would detect the disease.


It has been known for some time that increased production of sebum, a yellowish oily substance on the skin, is a hallmark of Parkinson's disease. Sebaceous glands normally help to moisturize the skin and hair, thereby also preventing sweat from evaporating (they are thus indirectly involved in temperature regulation). Sebum is a mixture of triglycerides, cholesterol, free fatty acids and waxy esters, as well as squalene, a product of cholesterol metabolism. It can be easily obtained from a skin swab and analyzed chemically.


Liquid chromatography-mass spectrometry (LC-MS) allows qualitative and quantitative analysis of a wide range of molecules found in complex mixtures and has been used for biofluids (blood, saliva, and cerebrospinal fluid) for many years. Now, last September, a group of researchers led by chemist Perdita Barran reported in the American Chemical Society journal JACS Au on their study of sebum samples from Parkinson's disease patients and controls. They identified a special lipid signature in more than 70 patients by the so-called paper spray ionization mass spectrometry (PS-MS), which allows direct analysis of very small molecules (50-800 Dalton).


The accuracy (specificity) of the assay is reported to be 90% (but this remains to be confirmed). In any case, the present study will further the development of biomarkers of Parkinson's disease and increase our understanding of altered metabolic pathways not only in diseased neural tissue but also in glandular cells. Moreover, Joy Milne's story has inspired many researchers to look for biomarkers in sebum in the first place, which could form an olfactory signature for disease. Recently, for example, Chinese colleagues have developed an artificial intelligence-based sensor that mimics our olfactory system and can identify different substances in the sebum of Parkinson's patients.


References:


Sinclair E et al. (2021) Metabolomics of sebum reveals lipid dysregulation in Parkinson’s disease. Nature Communications 12:1592


Sarkar D et al. (2022) Paper spray ionization ion mobility mass spectrometry of sebum classifies biomarker classes for the diagnosis of Parkinson’s disease. JACS Au 2:2013


Image credit: iStock/DrAfter123

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