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

• Published in: Neurobiology of disease Vol. 192; p. 106413
• Main Authors: Imarisio, Alberto, Yahyavi, Isar, Avenali, Micol, Di Maio, Anna, Buongarzone, Gabriele, Galandra, Caterina, Picascia, Marta, Filosa, Asia, Gasparri, Clara, Monti, Maria Cristina, Rondanelli, Mariangela, Pacchetti, Claudio, Errico, Francesco, Valente, Enza Maria, Usiello, Alessandro
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-03-2024; Elsevier
• Subjects: Age at onset; Aging; D-serine; Gender medicine; LEDD; Parkinson's disease; Serum amino acids; Gender medicine; Parkinson's disease; Serum amino acids; ALS; 6-OHDA; L-Glu; L-Gln; Gly; CSF; L-DOPA; Aging; L-Asp; LEDD; HPLC; L-Asn; SR; Age at onset; D-serine; AD; D-Ser; CI; IQR; DAAO; PD; NMDAR; L-Ser; MPTP
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/j.nbd.2024.106413

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.
•Serum D-serine concentrations increase during aging in PD patients but not in HC.•D-serine level directly correlates with age at PD onset.•Antiparkinsonian drugs downregulate D-serine and other NMDAR-stimulating aminoacids.•D-serine levels are affected by PD diagnosis and sex.