Metabolite and lipoprotein profiles reveal sex-related oxidative stress imbalance in de novo drug-naive Parkinson’s disease patients
Authors: Meoni Gaia , Tenori Leonardo , Schade Sebastian , Licari Cristina , Pirazzini Chiara , Bacalini Maria Giulia , Garagnani Paolo , Turano Paola ,   PROPAG-AGEING Consortium, Molin Alessandra Dal , Bartoletti-Stella Anna , Gabellini Anna , Adarmes-Gómez Astrid Daniela , Scaglione Cesa Lorella Maria , Nardini Christine , Rosaria Cilea , Boninsegna Claudia , Sala Claudia , Giuliani Cristina , Tejera-Parrado Cristina , Macias Daniel , Buiza-Rueda Dolores , Williams Dylan , Zago Elisa , Provini Federica , Magrinelli Francesca , Mignani Francesco , Ravaioli Francesco , Valzania Franco , Sixel-Döring Friederike , Mengozzi Giacomo , Calandra-Buonaura Giovanna , Dimitri Giovanna Maria , Fabbri Giovanni , Houlden Henry , Huertas Ismael , Doykov Ivan , Hällqvist Jenny , Rodríguez Juan Francisco Martín , Jylhävä Juulia , Bhatia Kailash P. , Mills Kevin , Baldelli Luca , Xumerle Luciano , Sambati Luisa , Milazzo Maddalena , Broli Marcella , Maturo Maria Giovanna , Periñán-Tocino Maria Teresa , Carriòn-Claro Mario , Bonilla-Toribio Marta , Delledonne Massimo , Labrador-Espinosa Miguel A. , Pedersen Nancy L. , Mir Pablo , De Massis Patrizia , Cortelli Pietro , Guaraldi Pietro , Liò Pietro , Gómez-Garre Pilar , Clayton Robert , Escuela-Martin Rocio , Ortega Rosario Vigo , Capellari Sabina , Hägg Sara , Schreglmann Sebastian R. , De Luca Silvia , Spasov Simeon , Nassetti Stefania Alessandra , Macrì Stefania , Azevedo Tiago , Heywood Wendy , Trenkwalder Claudia , Franceschi Claudio , Mollenhauer Brit , Luchinat Claudio 
Published: February 2022

Parkinson’s disease (PD) is the neurological disorder showing the greatest rise in prevalence from 1990 to 2016. Despite clinical definition criteria and a tremendous effort to develop objective biomarkers, precise diagnosis of PD is still unavailable at early stage. In recent years, an increasing number of studies have used omic methods to unveil the molecular basis of PD, providing a detailed characterization of potentially pathological alterations in various biological specimens. Metabolomics could provide useful insights to deepen our knowledge of PD aetiopathogenesis, to identify signatures that distinguish groups of patients and uncover responsive biomarkers of PD that may be significant in early detection and in tracking the disease progression and drug treatment efficacy. The present work is the first large metabolomic study based on nuclear magnetic resonance (NMR) with an independent validation cohort aiming at the serum characterization of de novo drug-naive PD patients. Here, NMR is applied to sera from large training and independent validation cohorts of German subjects. Multivariate and univariate approaches are used to infer metabolic differences that characterize the metabolite and the lipoprotein profiles of newly diagnosed de novo drug-naive PD patients also in relation to the biological sex of the subjects in the study, evidencing a more pronounced fingerprint of the pathology in male patients. The presence of a validation cohort allowed us to confirm altered levels of acetone and cholesterol in male PD patients. By comparing the metabolites and lipoproteins levels among de novo drug-naive PD patients, age- and sex-matched healthy controls, and a group of advanced PD patients, we detected several descriptors of stronger oxidative stress.