Elevated plasma levels of D-serine in some patients with amyotrophic lateral sclerosis

Abstract

D-serine is an endogenous co-agonist with glutamate for activation of the N-methyl-D-aspartate receptor (NMDAR). D-serine exacerbates neuronal death and is elevated in the spinal cord from patients with sporadic/familial ALS. The present study was undertaken to examine whether plasma levels of D-serine of patients with ALS are different from those of healthy controls. Levels of D-serine in plasma (30 patients and 30 controls) were measured by high-performance liquid chromatography mass spectrometry. Plasma levels of D-serine in ALS patients (mean 39.27 ± 28.61 ng/ml) were significantly higher (p = 0.0293) than those of healthy control subjects (mean 21.07 ± 14.03 ng/ml) as well as previously reported values for healthy controls; ∼43% of patients had plasma D-serine levels that were 2 to 4-folds higher than those of controls. There was no association of plasma D-serine levels with disability, the duration of disease or with the age of subjects. In conclusion, we show that D-serine levels are elevated in the plasma of some ALS patients. Since D-serine serves as a co-agonist/activator of NMDAR, increases in D-serine could have a direct influence on glutamatergic neurotransmission and potentially contribute to excitotoxicity in some ALS patients.

Keywords:

• Amyotrophic lateral sclerosis
• mass spectrometry
• D-serine

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This study was supported by a Wesley Medical Research Grant awarded to PA McCombe and RD Henderson and by a grant from MND Research Australia to PA McCombe.