Parkinson’s disease (PD) is a progressive, neurodegenerative disease that presents with significant motor symptoms, for which there is no diagnostic chemical test. We have serendipitously identified a hyperosmic individual, a “Super Smeller” who can detect PD by odor alone, and our early pilot studies have indicated that the odor was present in the sebum from the skin of PD subjects. Here, we have employed an unbiased approach to investigate the volatile metabolites of sebum samples obtained noninvasively from the upper back of 64 participants in total (21 controls and 43 PD subjects). Our results, validated by an independent cohort ( n =31), identified a distinct volatiles-associated signature of PD, including altered levels of perillic aldehyde and eicosane, the smell of which was then described as being highly similar to the scent of PD by our “Super Smeller”.
Parkinson’s disease (PD) is a progressive neurodegenerative disorder, which is characterised by degeneration of distinct neuronal populations, including dopaminergic neurons of the substantia nigra. Here, we use a metabolomics profiling approach to identify changes to lipids in PD observed in sebum, a non-invasively available biofluid. We used liquid chromatography-mass spectrometry (LC-MS) to analyse 274 samples from participants (80 drug naïve PD, 138 medicated PD and 56 well matched control subjects) and detected metabolites that could predict PD phenotype. Pathway enrichment analysis shows alterations in lipid metabolism related to the carnitine shuttle, sphingolipid metabolism, arachidonic acid metabolism and fatty acid biosynthesis. This study shows sebum can be used to identify potential biomarkers for PD.
In this study we explore the use of collision cross section distributions to allow comparability of IM-MS data for proteins on different instruments. We present measurements on seven standard proteins across three IM-MS configurations, namely an Agilent 6560 IM QToF, a Waters Synapt G2 possessing a TWIMS cell and a modified Synapt G2 possessing an RF confining linear field drift cell. Mobility measurements were taken using both He and N 2 as the drift gases. To aid comparability across instruments and best assess the corresponding gas-phase conformational landscapes of the protein 'standards' we present the data in the form of averaged collision cross section distributions. File list (5) download file view on ChemRxiv France_ccs_compare_SI_sub.pdf (4.79 MiB) download file view on ChemRxiv France_ccs_compare_sub.pdf (1.49 MiB) download file view on ChemRxiv France_ccs_compare_paper_version2.pdf (0.99 MiB) download file view on ChemRxiv France_ccs_compare_SI_version2.docx (6.13 MiB) download file view on ChemRxiv TWIMS_CCS_Calibration_plots.pptx (226.74 KiB)
Parkinson's disease (PD) is a progressive, neurodegenerative disease that presents with significant motor symptoms, for which there is no diagnostic test (1-3). We have serendipitously identified a hyperosmic individual, a 'Super Smeller' that can detect PD by odor alone, and our early pilot studies have indicated that the odor was present in the sebum from the skin of PD subjects(4). Here, we have employed an unbiased approach to investigate the volatile metabolites of sebum samples obtained noninvasively from the upper back of 64 participants in total (21 controls and 43 PD subjects). Our results, validated by an independent cohort, identified a distinct volatiles-associated signature of PD, including altered levels of perillic aldehyde and eicosane, the smell of which was then described as being highly similar to the scent of PD by our 'Super Smeller'.Physicians in ancient times, including Hippocrates, Galenus, and Avicenna, used odor as a diagnostic tool. Although the olfactory skills of physicians are not routinely used in modern medicine, it is well documented that a number of conditions, predominantly metabolic and infectious diseases, are associated with a unique odor(5), but there is scant evidence for odors as symptoms of neurodegenerative disorders. Joy Milne, a Super Smeller whose Recently, TD-GC-MS has been used as a volatilome analysis platform for the detection of compounds from bacteria implicated in ventilator associated pneumonia(12), for differentiation between odors due to human and animal decomposition(17), as well as aerosol detection of the fumes from e-cigarettes(18). This versatility of TD-GC-MS for samples from many sources renders it highly suitable for use in identifying the metabolites
Parkinson’s disease (PD) is a progressive neurodegenerative disorder that does not currently have a robust clinical diagnostic test. Nonmotor symptoms such as skin disorders have long since been associated with the disease, and more recently a characteristic odor emanating from the skin of people with Parkinson’s has been identified. Here, dynamic head space (DHS) thermal desorption (TD) gas chromatography–mass spectrometry (GC-MS) is implemented to directly measure the volatile components of sebum on swabs sampled from people with Parkinson’s—both drug naïve and those on PD medications ( n = 100) and control subjects ( n = 29). Supervised multivariate analyses of data showed 84.4% correct classification of PD cases using all detected volatile compounds. Variable importance in projection (VIP) scores were generated from these data, which revealed eight features with VIP > 1 and p < 0.05 which all presented a downregulation within the control cohorts. Purified standards based on previously annotated analytes of interest eicosane and octadecanal did not match to patient sample data, although multiple metabolite features are annotated with these compounds all with high spectral matches indicating the presence of a series of similar structured species. DHS-TD-GC-MS analysis of a range of lipid standards has revealed the presence of common hydrocarbon species rather than differentiated intact compounds which are hypothesized to be breakdown products of lipids. This replication study validates that a differential volatile profile between control and PD cohorts can be measured using an analytical method that measures volatile compounds directly from skin swabs.
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