Plasma glutamate and glycine levels in patients with amyotrophic lateral sclerosis

Defective glutamate (Glu) metabolism and glutamate excitotoxicity have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Glycine (Gly), the main inhibitory neurotransmitter, has been shown to potentiate excitatory transmission. In the present study, the levels of Glu and Gly in fasting plasma were measured by high performance liquid chromatography (HPLC) in 20 healthy volunteers and in 65 untreated ALS patients. Increased plasma Glu levels were observed in ALS (p = 0.05), correlating with longer disease duration (p = 0.03, beta=0.34) and male gender (p=0.02). Furthermore, the increase was found only in the spinal subtype of the disease (p = 0.03), while in the bulbar subtype, no significant increase was noted. As regards plasma Gly, no difference was observed between patients and controls; however female patients had higher levels than males. The above results are compatible with the "glutamate hypothesis" of ALS and suggest that the spinal and bulbar-onset subtypes of the disease may be biochemically different.