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

Parkinson’s disease (PD) is a progressive condition resulting in dopaminergic nigrostriatal neuronal death. Several evidence suggest that beyond dopaminergic system other neurotransmitters are involved in PD. In particular, molecular alterations occurring at ionotropic N-methyl-D-aspartate receptors (NMDARs) contribute to appearance of the disease features. Among neurotransmitters involved in glutamatergic system, D-serine (D-Ser) plays a crucial role acting as NMDARs co-agonist. A previous study carried out on preclinical models of PD, showed increased levels of D-Ser as well as of its metabolic precursor, L-serine (L-Ser) in the rostral putamen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys. Interestingly, these data were consistent with a clinical study showing an increase in serine enantiomers in cerebrospinal fluid and caudate putamen of PD patients. Considering these evidence, we investigated serum levels of D- and L-Ser as well as other NMDAR-related amino acids in a cohort of 83 PD patients compared to 41 healthy controls (HC) through High Performance Liquid Chromatography (HPLC). Moreover, we investigated the correlation between these amino acids, clinical-demographic features and levodopa equivalent daily dose (LEDD). Our results show a positive correlation of D-Ser and D-/Total Ser ratio with age in PD patients and age at onset. Furthermore, we found that antiparkinsonian treatment negatively affects the serum levels of D-Ser and other NMDAR-related excitatory amino acids in a dose-dependent manner. In addition, we observed a statistically significant increase of D-Ser in female PD patients compared to HC.Overall, these findings propose that serum D-serine and D-/Total serine may represent a potential biomarker of PD.