The oily secretions from skin could carry the signatures of Parkinson’s disease.
In 2019, researchers revealed that Joy Milne, who has a particularly keen sense of smell, was able to identify people with Parkinson’s disease by the odor of clothes they had worn. In that work, Perdita Barran of the University of Manchester and coworkers used gas chromatography mass spectrometry to analyze sebum, the oily secretions from sebaceous glands in the skin, and identify the volatile components that recreated the smell (ACS Cent. Sci. 2019, DOI: 10.1021/acscentsci.8b00879). Barran, Milne, and coworkers recently validated that volatile sebum components in people with Parkinson’s disease did indeed differ from controls using a larger cohort of people (ACS Cent. Sci. 2021, DOI: 10.1021/acscentsci.0c01028).
But a sniff test is not a particularly practical or quantitative way to detect biomarkers of Parkinson’s disease. Today, Parkinson’s is diagnosed based on a collection of symptoms, such as tremors. “Parkinson’s disease research desperately needs biomarkers,” says Ulf Dettmer, who studies Parkinson’s disease at Harvard Medical School. The new study suggests “an unexpected, yet compelling and easily available source, for biomarkers,” he says.
To come up with an approach more amenable to clinical labs, Barran and her collaborators have now used liquid chromatography mass spectrometry to identify nonvolatile lipids in sebum that are associated with Parkinson’s (Nat. Commun. 2021, DOI: 10.1038/s41467-021-21669-4). They used skin swabs from three groups of people: those with Parkinson’s who had not yet received Parkinson’s medication, others who had received drug treatment, and a control group who did not have Parkinson’s. “We wanted to make sure that what we measured was not the effect of medication,” Barran says.
The analysis revealed 10 metabolites, including ceramides and fatty acyls, that differed significantly from the control cohort in both the drug-naive and medicated populations. Conclusive identification of the individual metabolites is challenging because many lipids have multiple isomers that differ only in the location of a double bond. However, the findings point to several lipid pathways with altered lipid levels in both drug-naive and drug-treated people with Parkinson’s. These pathways include the carnitine shuttle, which is involved in fatty acid oxidation, and sphingolipid metabolism, which is involved in cell signaling.
Variations in lipid pathways between the two groups of people with Parkinson’s could be related to disease progression. “This work starts to show that with relatively simple mass spectrometry and definitely simple sampling we’re able to learn how the disease is progressing in individuals,” Barran says. The sampling is noninvasive, and the swabs can be easily stored. Barran and coworkers are developing a clinical assay in which they target specific lipids rather than doing an untargeted lipid analysis. They think such an assay could help understand disease progression.