Study On The Relationship Of Plasma N-acetyl Aspartate Level Andalzheimer’s Disease

Research Background:Alzheimer’s disease (AD) is a neuronal degeneration disease with progressivelycognitive impairment.. N-acetyl aspartic acid(NAA) is an important biomarker offunctional integrity and vitality in neurons. In vivo proton magnetic resonancespectroscopy(1H-MRS) studies indicate that NAA level decreases in specific brainareas of the patients with AD, but the high technical standard, increasing medicalexpenditure and operational difficulties in1H-MRS limit its potential for clinicalapplication.Objective:1.To establish a method to detect N-acetyl aspartic acid (NAA)level inplasma,with high liquid chromatography-mass spectrometry(LC-MS) combinationanalysis method.2.To compare the changes of plasma NAA level in AD patients and normalhealthy people, and to explore the correlation between the plasma NAA level andNAA concentration in the brain detected by1H-MRS technology, in order to makeclear whether the concentration of plasma NAA can be used as a plasma marker inAD.Methods:1.An external standard method of LC-MS was applied to establish thequantitative standard curve of NAA level in plasma. Validation data on quantitativeanalysis of NAA level in plasma, including linear range, correlation coefficient,precision, recovery and detection limit had been studied.2. Plasma NAA concentrations of23AD patients and29normal controls weremeasured and their clinical data were also recorded. Brian NAA level in bilateral hippocampus was detected with1H-MRS in7AD patients and7age-matchedcontrols at the same time. NAA/Cr, NAA/Ch and Ch/Cr ratio between the twogroups were compared. The correlation between the MMSE score,the age andNAA/Cr, NAA/Ch and Ch/Cr ratio was analyzed..Results:1. Plasma NAA level in patients with AD (12.49±3.4924μmol/L) wassignificantly higher than healthy controls (10.62±3.6643umol/L)(p﹤0.05,Mann-Whitney test). In AD group, there was no apparent difference incorrelation between plasma NAA levels and age(p﹥0.05). In healthy controls, theNAA level in the younger groups (12.70±3.6552umol/L) was significantly higherthan the older group(8.68±2.4717umol/L)(p﹤0.05,Mann-Whitney test). Theplasma NAA level between the two groups had no significant differences in gender(p﹥0.05，Mann-Whitney test).④In AD group, there was no correlations between theconcentration of NAA and MMSE score, course of disease, age. While in the controlgroup, the age and the plasma level of NAA had clearly negative correlation (r=0.77, p﹤0.001,Spearman rank correlation).2. The NAA/Ch, NAA/Cr ratio in bilateral hippocampus between AD andcontrol group had significant differences (P﹤0.05), but left and right sides of Ch/Crratio between the two groups had no obvious difference (P﹥0.05). The correlationsbetween MMSE score, age and the bilateral sides of NAA/Ch, NAA/Cr and Ch/Crratio had no significant differences (p﹥0.05).Conclusions:1.LC-MS is a simple, rapid and accurate quantitative analysis method fordetection of plasma NAA.2. Plasma NAA level in patients with AD is increased，but NAA level is reducedin the brain.