Impact of plasma transaminase levels on the peripheral blood glutamate levels and memory functions in healthy subjects

Abstract

Background & aimsBlood aspartate aminotransferase (AST) and alanine transaminase (ALT) levels are the most frequently reliable biomarkers of liver injury. Although AST and ALT play central roles in glutamate production as transaminases, peripheral blood levels of AST and ALT have been regarded only as liver injury biomarkers. Glutamate is a principal excitatory neurotransmitter, which affects memory functions in the brain. In this study, we investigated the impact of blood transaminase levels on blood glutamate concentration and memory.MethodsPsychiatrically, medically, and neurologically healthy subjects (n = 514, female/male: 268/246) were enrolled in this study through local advertisements. Plasma amino acids (glutamate, glutamine, glycine, d-serine, and l-serine) were measured using a high performance liquid chromatography system. The five indices, verbal memory, visual memory, general memory, attention/concentration, and delayed recall of the Wechsler Memory Scale-Revised were used to measure memory functions.ResultsBoth plasma AST and ALT had a significant positive correlation with plasma glutamate levels. Plasma AST and ALT levels were significantly negatively correlated with four of five memory functions, and plasma glutamate was significantly negatively correlated with three of five memory functions. Multivariate analyses demonstrated that plasma AST, ALT, and glutamate levels were significantly correlated with memory functions even after adjustment for gender and education.ConclusionsAs far as we know, this is the first report which could demonstrate the impact of blood transaminase levels on blood glutamate concentration and memory functions in human. These findings are important for the interpretation of obesity-induced metabolic syndrome with elevated transaminases and cognitive dysfunction.

Association of Altered Liver Enzymes With Alzheimer Disease Diagnosis, Cognition, Neuroimaging Measures, and Cerebrospinal Fluid Biomarkers

“…52 Glutamate acts as a neurotransmitter in approximately two-thirds of the synapses in neocortical and hippocampal pyramidal neurons and thus is involved in memory and cognition via long-term potentiation. 53 In a sample of healthy adults, plasma ALT and AST levels were significantly positively correlated with plasma glutamate levels, 5,54 which indicates that lower levels of ALT will decrease glutamate levels in plasma. Based on evidence from earlier studies that peripheral blood levels of glutamate are positively correlated with levels of glutamate in the CSF 55 and studies that reported lower levels of glutamate in patients with AD compared with controls in both blood 56 and brain tissues, 36,57,58,59 we can infer that lower levels of ALT or AST may affect glutamate levels in AD.…”

Associations of Serum Liver Function Markers With Brain Structure, Function, and Perfusion in Healthy Young Adults

“…Previous work has established that serum ALT level is associated with cognition in healthy and clinical populations (62)(63)(64). Besides, it is generally accepted that the SFG contributes to higher cognitive functions and particularly to working memory (65,66).…”

The recency ratio is associated with reduced CSF glutamate in late-life depression

“…However, a recent study has reported correlations between plasma glutamate levels and memory scores in a large cohort of over 500, young, neurologically healthy individuals (Kamada et al, 2016). Unlike in the present report, the study by Kamada et al showed negative correlations between glutamate levels and memory proficiency (Japanese Wechsler Memory Scale-Revised: verbal memory, general memory & delayed recall), albeit with fairly small effect sizes.…”