Blood d-serine levels correlate with aging and dopaminergic treatment in Parkinson's disease.

We recently described increased D- and l-serine concentrations in the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys, the post-mortem caudate-putamen of human Parkinson's disease (PD) brains and the cerebrospinal fluid (CSF) of de novo living PD patients. However, data regarding blood D- and l-serine levels in PD are scarce. Here, we investigated whether the serum profile of D- and l-serine, as well as the other glutamate N-methyl-d-aspartate ionotropic receptor (NMDAR)-related amino acids, (i) differs between PD patients and healthy controls (HC) and (ii) correlates with clinical-demographic features and levodopa equivalent daily dose (LEDD) in PD. Eighty-three consecutive PD patients and forty-one HC were enrolled. PD cohort underwent an extensive clinical characterization. Serum levels of D- and l-serine, L-glutamate, l-glutamine, l-aspartate, L-asparagine and glycine were determined using High Performance Liquid Chromatography. In age- and sex-adjusted analyses, no differences emerged in the serum levels of d-serine, l-serine and other NMDAR-related amino acids between PD and HC. However, we found that d-serine and D-/Total serine ratio positively correlated with age in PD but not in HC, and also with PD age at onset. Moreover, we found that higher LEDD correlated with lower levels of d-serine and the other excitatory amino acids. Following these results, the addition of LEDD as covariate in the analyses disclosed a selective significant increase of d-serine in PD compared to HC (Δ ≈ 38%). Overall, these findings suggest that serum d-serine and D-/Total serine may represent a valuable biochemical signature of PD.

Informations de copyright

Copyright © 2024. Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Enza Maria Valente reports financial support was provided by Cariplo Foundation. Enza Maria Valente reports financial support was provided by Ministry of Health. Alessandro Usiello reports financial support was provided by Minister of University and Research. Micol Avenali reports a relationship with Aligning Science Across Parkinson's that includes: board membership. Micol Avenali reports a relationship with Bial that includes: speaking and lecture fees. Micol Avenali reports a relationship with Zambon SpA that includes: speaking and lecture fees. Micol Avenali reports a relationship with Ministry of Health that includes: funding grants. Enza Maria Valente reports a relationship with Aligning Science Across Parkinson's that includes: board membership and funding grants. Enza Maria Valente reports a relationship with Ministry of Health that includes: funding grants. Enza Maria Valente reports a relationship with Telethon Foundation that includes: funding grants. Enza Maria Valente reports a relationship with Pierfranco and Luisa Mariani Foundation that includes: funding grants. Enza Maria Valente reports a relationship with European Commission (Era-net Neuron) that includes: funding grants. Enza Maria Valente is Associate Editor of Journal of Medical Genetics; is Genetics Section Editor of Pediatric Research, of The Cerebellum, and of Neurological Sciences; is member of the Editorial Board of Movement Disorders Clinical Practice. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.