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

Introduction: We recently described increased D- and L-serine concentrations in the striatum of MPTP-treated monkeys and human Parkinson’s disease (PD) brains and in the CSF of de novo living PD patients compared to controls. However, data regarding peripheral D-serine levels in PD are scarce. Here we assessed whether the serum levels of serine enantiomers and the other NMDA receptor-related aminoacids (i) differ between PD patients and HC and (ii) correlate with demographic, clinical features and dopaminergic treatment in PD. Methods: We recruited 83 consecutive PD patients and 41 age-matched healthy controls (HC). PD cohort underwent an extensive motor, cognitive, quality of life and antiparkinsonian treatment characterization. The serum levels of D- and L-serine, L-glutamate, L-glutamine, L-aspartate, L-asparagine and glycine were determined using High Performance Liquid Chromatography. Results: In age- and sex-adjusted analyses, no differences emerged in the serum levels of D-serine, L-serine or the other NMDA receptor-stimulating aminoacids between PD and HC. D-serine and D-/Total serine ratio positively correlated with age in PD but not in HC (r=0.313, p=0.004 and r=0.311, p=0.004, respectively). Moreover, we found that (i) D-serine and D-/Total serine, but not the other neuroactive aminoacids, increase with older age at PD onset (r=0.379, p<0.001 and r=0.325, p=0.003, respectively); (ii) higher LEDD correlate with lower levels of D-serine (r =-0.248, p=0.027) and the other excitatory aminoacids; (iii) MDS-UPDRS-III positively correlate with glycine (r=0.241, p=0.033). Finally, the addition of LEDD as covariate disclosed higher serum D-serine in PD compared to HC (Δ=38.7%; p=0.038). Conclusions: increased serum D-serine levels represent a putative biochemical signature of PD. The positive correlation between D-serine and age at PD onset supports the hypothesis that D-serine may play a neuroprotective role in PD by delaying the onset of the disease.