A New Way to Detect Parkinson’s—Right from the Ear

Parkinson’s disease is a neurodegenerative condition that affects motor and cognitive function, resulting in a range of movement and mental health symptoms.¹ Most current treatments only slow disease progression, but with estimates putting the 2050 prevalence at over 25 million people,² there is a drive to achieve earlier intervention. At present, diagnosis relies on clinical rating scales, neural imaging, and genetic testing,³ but there is a pressing need for screening options that are easy, fast, and low cost—and this is driving the search for biomarkers.

In 2016 it was reported that Joy Milne, the wife of a Parkinson’s patient, could detect the condition through smell.⁴ This was due to her having hyperosmia, which causes heightened sensitivity to subtle odors that others might miss. Preliminary tests pinpointed the odor to areas of high sebum production such as the upper back and forehead. Sebum is a waxy, lipid-rich biofluid, and overproduction is a known non-motor symptom of Parkinson’s.⁵

These findings inspired the use of specific volatile organic compounds (VOCs) for Parkinson’s diagnosis. Previous studies have also used mass spectrometry to reveal a unique volatilome associated with Parkinson’s, which could prove extremely useful for non-invasive diagnosis.⁶ But since not all of us are super-smellers like Mrs. Milne, there is a need to develop biosensors that can transform these snippets of biochemical information into an analytically useful signal. A 2021 study used supervised multivariate analyses of VOC data to achieve correct classification of cases in 84% of cases, with sebum swabs taken from the upper back.⁷ But a critical issue is that exposure to air pollution and humidity changes the composition of sebum on the skin, making it an unreliable testing medium.

A Cleaner Signal: VOCs from the Ear Canal

Now, new work published in Analytical Chemistry proposes a diagnostic model based on VOCs from ear canal secretions, where the sebum is kept away from the elements.⁸ The team used gas chromatography–mass spectrometry to examine samples from patients, and they were able to identify four VOC components as biomarkers with statistically significant differences between people with and without Parkinson’s. The research builds on earlier work from members of the same team to develop an artificial Intelligent Olfactory System.⁹

The researchers identified the following four VOC components as being linked to Parkinson’s:

• Ethylbenzene
• 4-ethyltoluene
• Pentanal
• 2-pentadecyl-1,3-dioxolane

Diagnostic models based on these VOC components demonstrate strong capability in identifying and classifying people with Parkinson’s. To enhance the accuracy and efficiency of the PD diagnostic model, the study introduced a protocol for extracting features from chromatographic data. By integrating gas chromatography–surface acoustic wave sensors with a convolutional neural network model, the system was able to achieve accuracy of over 94%.

The authors are hopeful that further enhancements to the diagnostic model could pave the way for a promising new diagnostic solutions—and the possibility of a non-invasive point-of-care device. “The next step is to conduct further research at different stages of the disease, in multiple research centers and among multiple ethnic groups, in order to determine whether this method has greater practical application value,” notes Corresponding Author Hao Dong in a recent press release.

Ear Wax as a Diagnostic Goldmine

Ear wax, or cerumen, is a complex lipid-rich mixture made up from dead skin cells, hair, and oily secretions from the sebaceous and apocrine sweat glands within the ear canal.¹⁰ It contains the most concentrated levels and highest diversity of surface accessible lipids in the human body, and its physical characteristics are associated with several disorders. For example, increased waxy elements are found in people with psoriasis, whereas dry wax is reported in cystic fibrosis, and dark brown or black wax occurs with alkaptonuria.¹¹ Other VOCs in ear wax have been tested for their ability to differentiate carcinoma, lymphoma, and leukemia, as well as Ménière’s disease, with good results reported so far.¹²

Of course, there are several challenges, including the need to establish a norm from which chemical changes as a function of different metabolic states can be measured. There are also limitations around reliability, precision, selectivity, and stability in continuous monitoring—but advancements in nanotechnology could be the answer.¹³ What is clear is that there is value in sniffing out more opportunities in this field. With Parkinson’s, many people are not diagnosed until late in the disease, limiting the options for intervention. In the future, these non-invasive approaches could help identify those at risk earlier—and may even help drive the development of a much-needed cure.

References

1. World Health Organization. https://www.who.int/news-room/fact-sheets/detail/parkinson-disease
2. Su, D. et al. Projections for prevalence of Parkinson’s disease and its driving factors in 195 countries and territories to 2050: modelling study of Global Burden of Disease Study 2021. BMJ 2025, 388.
3. Postuma, R. B. et al. MDS Clinical Diagnostic Criteria for Parkinson’s Disease: MDS-PD Clinical Diagnostic Criteria. Mov. Disord. 2015, 30 (12), 1591–1601.
4. Morgan, J. Joy of Super Smeller: Sebum Clues for PD Diagnostics. Lancet Neurol. 2016, 15 (2), 138–139.
5. Ravn, A.- H., et al. Skin disorders in Parkinson’s disease: potential biomarkers and risk factors. Clin. Cosmet. Invest. Dermatol. 2017, 10, 87–92.
6. Trivedi, D. K. et al. Discovery of Volatile Biomarkers of Parkinson’s Disease from Sebum. ACS Cent Sci. 2019, 20, 5(4), 599–606.
7. Sinclair, E. et al. Validating Differential Volatilome Profiles in Parkinson’s Disease. ACS Cent. Sci. 2021, 7, 2, 300–306.
8. Chen, X. et al. An Artificial Intelligence Olfactory-Based Diagnostic Model for Parkinson’s Disease Using Volatile Organic Compounds from Ear Canal Secretions. Anal. Chem. 2025, 97, 24, 12633–12641.
9. Fu, W. et al. Artificial Intelligent Olfactory System for the Diagnosis of Parkinson’s Disease. ACS Omega 2022, 7, 5, 4001–4010.
10. Alvord, L. S.; Farmer, B. L. Anatomy and orientation of the human external ear. J. Am. Acad. Audiol. 1997, 8, 383– 39030.
11. Hanger, H. C. and Mulley, G. P. Cerumen: Its fascination and clinical importance: A review. J. R. Soc. Med. 1992, 85, 346–349.
12. Coon, A. M. et al. Mass Spectrometric Interrogation of Earwax: Toward the Detection of Ménière’s Disease. ACS Omega 2023, 8, 30, 27010–27023.
13. Jalal, A. H. et al. Prospects and Challenges of Volatile Organic Compound Sensors in Human Healthcare. ACS Sens. 2018, 3 (7), 1246–1263.