Assessment of plasma N-acetyl aspartic acid by Liquid chromatography-mass spectrometry in patients with Alzheimer’s disease

Objective: Alzheimer’s disease (AD) is a neural degenerative disease with progressive cognitive impairment. N-acetyl aspartic acid (NAA) is an important biomarker for assessing neuronal activity and brain cells metabolic abnormalities. This investigation is aimed to establish a liquid chromatography-mass spectrometry (LC-MS) method for measuring plasma NAA level, in order to make clear whether plasma NAA level can be used as a plasma biomarker in AD. Methods: A LC-MS method was established and validated for quantitative analysis of plasma NAA, and the plasma NAA concentrations of 23 AD patients and 36 healthy controls were analyzed and compared. In addition, the bilateral hippocampus NAA levels in 7 AD patients and 7 age-matched healthy controls were comparative analyzed by 1H-MRS method, and corresponding correlation analyses were also performed. Results: An optimized LC-MS method was applied for measuring plasma NAA levels. Plasma NAA levels were significantly higher in AD patients (14.02±2.324 μM) than controls (11.12±2.67 μM) (P<0.01), and statistically different between different age group in both AD patients and healthy controls (P<0.05), with a significantly negative correlation with age in healthy controls (r = -0.462, P = 0.008). The ratios of NAA/Ch, NAA/Cr in both hippocampus measured by 1H-MRS were significantly decreased in AD patients than in controls (P<0.05), and there were no statistical correlations between plasma NAA concentrations and NAA/Ch, NAA/Cr and Ch/Cr ratios in the selected 7 AD patients. Conclusions: LCMS method can be used as a simple, rapid and accurate quantitative analysis method for plasma NAA measurement. As NAA level increased in plasma and decreased in the brain, the plasma NAA level could be used as an index for early clinical AD screening.