L-glutamate, L-arginine and L-citrulline levels in cerebrospinal fluid of Parkinson's disease, multiple system atrophy, and Alzheimer's disease patients.

Alterations in neuronal nitric oxide (NO) production may play a role in the pathophysiology of Parkinson's disease (PD) Alzheimer's disease (AD), and multiple system atrophy (MSA). The biosynthesis of NO is dependent on the availability of L-arginine, the substrate for NO-synthase (NOS), and on L-glutamate, which stimulates NO synthesis via the NMDA receptor. In this process L-citrulline is formed. We measured the levels of these amino acids in cerebrospinal fluid (CSF) of 108 PD patients, 12 AD patients, 15 MSA patients and 21 healthy subjects. A slight but statistically significant elevation of CSF L-citrulline was found in MSA patients, while CSF L-glutamate was found to be significantly decreased in AD patients. We found no significant changes in L-arginine levels. Although the relation between the CSF levels of these amino acids and neuronal NO production is still unclear, our findings suggest that AD is associated with a decrease in NO synthesis.