Plasma Metabolomics Profiles in Prodromal and Clinical Parkinson's Disease

Abstract

BackgroundThe long prodromal phase of Parkinson's disease (PD) and the link the disease has with metabolic factors suggest that metabolomics could help identify affected individuals at early stages.ObjectiveThe goal was to examine whether plasma metabolomic profiles could identify individuals in the prodromal and clinical phase of PD.MethodsWe quantified and compared the plasma metabolomic profiles of 922 individuals with PD who provided blood samples at a median of 11 years before (n = 809) or 2 years after (n = 113) disease diagnosis to that of matched controls, all selected from three established cohort studies (Nurses' Health Study, Health Professionals Follow‐up Study, and Cancer Prevention Study II). We used conditional logistic regression models and machine learning techniques to identify metabolites predicting prodromal and clinically manifest PD.ResultsSeveral metabolites, especially amino acids, acyl‐carnitines, and other lipids were nominally associated with PD since the years leading to disease diagnosis. Metabolites proposed as biomarkers of foods or care products tended to be associated with a higher PD risk closer to disease diagnosis. Metabolites reflecting higher intake of coffee, smoking, and acetaminophen tended to be associated with a lower PD risk over the course of the disease. Metabolomic profiles in prodromal samples were unable to accurately predict future clinical PD.ConclusionsMetabolic pathways related to the metabolism of amino acids and lipids may be involved in PD progression. Metabolomic differences may also result from behavioral changes and medical management, emphasizing the need to consider prodromal and clinical data in future studies. © 2025 International Parkinson and Movement Disorder Society.

Plasma Levels of Food-Derived Metabolites as Biomarkers of Parkinson’s Disease

“…The identification of reliable biomarkers for PD is crucial for early diagnosis, monitoring disease progression, and evaluating therapeutic interventions [ 4 ]. Recent research has highlighted the potential role of food-derived metabolites as accessible plasma biomarkers, which may reflect dietary influences, metabolic alterations, or interactions with genetic factors implicated in PD pathogenesis [ 5 , 6 ].…”

Plasma Levels of Food-Derived Metabolites as Biomarkers of Parkinson’s Disease

“…The identification of reliable biomarkers for PD is crucial for early diagnosis, monitoring disease progression, and evaluating therapeutic interventions [ 4 ]. Recent research has highlighted the potential role of food-derived metabolites as accessible plasma biomarkers, which may reflect dietary influences, metabolic alterations, or interactions with genetic factors implicated in PD pathogenesis [ 5 , 6 ].…”

Plasma Levels of Food-Derived Metabolites as Biomarkers of Parkinson’s Disease

“…The identification of reliable biomarkers for PD is crucial for early diagnosis, monitoring disease progression, and evaluating therapeutic interventions [ 4 ]. Recent research has highlighted the potential role of food-derived metabolites as accessible plasma biomarkers, which may reflect dietary influences, metabolic alterations, or interactions with genetic factors implicated in PD pathogenesis [ 5 , 6 ].…”

Plasma Levels of Food-Derived Metabolites as Biomarkers of Parkinson’s Disease

“…The identification of reliable biomarkers for PD is crucial for early diagnosis, monitoring disease progression, and evaluating therapeutic interventions [ 4 ]. Recent research has highlighted the potential role of food-derived metabolites as accessible plasma biomarkers, which may reflect dietary influences, metabolic alterations, or interactions with genetic factors implicated in PD pathogenesis [ 5 , 6 ].…”