Cerebrospinal fluid concentrations of functionally important amino acids in patients with Alzheimer's disease compared to mild cognitive impairment

Background: Cerebrospinal fluid (CSF) biomarkers play an important role in the differenzial diagnosis of neurodgenerative diseases such as Alzheimer's disease (AD) and its postulated precursor stage mild cognitive impairment (MCI). While CSF tau-protein, phospho-tau-protein and beta-amyloid have become part of the diagnostic process in clinical routine, the importance of several other biomarkers remains quite unclear. Among these, amino acids have been studied in clinical conditions mostly other than AD and, to our knowledge, never in MCI. Methods In patients with AD (n=14) and MCI (n=13) we now determined CSF levels of 36 different amino acids by High Performance Liquid Chromatography. Results: We found that 9 amino acids (urea,threonine,serine,glutamate,citrulline,alpha-amino-butyric acid,ornithine,ammonia and arginine) were significantly elevated in the CSF of AD compared to MCI patients. Conclusions: As all these elevated amino acids are related to known specific biochemical mechanisms in the aging brain, our findings may indicate such compensatory mechanisms in the CSF of AD and MCI patients. There were no direct indications of reduced antioxidative capacity from the CSF levels of carnosine or the precursors of glutathione (glycine, glutamate, cyst(e)ine), though the increased glutamate observed may inhibit the uptake of cyste(i)ne which may limit glutathione synthesis. Furthermore, MCI patients are very likely to present early signs of this compensatory activation.