Metabolomic breath analysis identifies lipid biomarker candidates in Parkinson's disease

An unedited manuscript reports untargeted metabolomics of exhaled breath from 73 Parkinson's patients and 90 controls that highlighted seven putative lipid metabolites differing between groups; five of these also appeared in some unaffected LRRK2 variant carriers, and the authors state MS/MS confirmation is still needed.

An unedited manuscript posted ahead of final publication describes an untargeted metabolomics study using exhaled breath to search for biomarkers of Parkinson's disease. The authors frame breath as a noninvasive sampling route that they suggest may address a need for earlier and more accessible PD biomarkers. Breath and blood plasma samples were analysed by extreme‑resolution FT‑ICR‑MS and compared across patient groups, unaffected carriers, and controls. The manuscript is unedited and will undergo further revision before final publication. Key findings: - The study analysed breath samples from 73 PD patients (LRRK2 n=12, GBA1 n=35, PRKN n=6, idiopathic n=20), 4 unaffected LRRK2 pathogenic variant carriers, and 90 controls. - Analyses used extreme‑resolution Fourier‑transform ion cyclotron resonance mass spectrometry (FT‑ICR‑MS) on exhaled breath and compared findings with plasma metabolomics data. - Biostatistical models reportedly distinguished PD patients from healthy controls with an out‑of‑bag (OOB) error below 1%. - Seven putative metabolites were identified in breath from PD patients regardless of genetic status: tricosanoic acid, docosanamide, eicosanoic acid, homophytanic acid, nonadecyl‑MG, stearic acid, and palmitic acid. - Five of these metabolites were also reported in unaffected LRRK2 carriers versus controls, and most proposed structures are intermediates in fatty acid metabolism. - The authors note that the proposed metabolite identities require MS/MS confirmation. Summary: Breath metabolomics in this report produced candidate lipid markers that differentiated Parkinson's patients from controls and showed overlap with findings in some unaffected LRRK2 carriers. The work points to breath as a possible source of noninvasive biomarker candidates, but metabolite identities and their relevance need MS/MS confirmation and further validation. The manuscript is an early, unedited report and will be revised before final publication.