High performance liquid chromatography determination of l-glutamate, l-glutamine and glycine content in brain, cerebrospinal fluid and blood serum of patients affected by Alzheimer’s disease

• Published in: Amino acids Vol. 53; no. 3; pp. 435 - 449
• Main Authors: Nuzzo, Tommaso, Mancini, Andrea, Miroballo, Mattia, Casamassa, Alessia, Di Maio, Anna, Donati, Giorgia, Sansone, Giulia, Gaetani, Lorenzo, Paoletti, Federico Paolini, Isidori, Andrea, Calabresi, Paolo, Errico, Francesco, Parnetti, Lucilla, Usiello, Alessandro
• Format: Journal Article
• Language: English
• Published: Vienna Springer Vienna 01.03.2021; Springer Nature B.V
• Subjects: Alzheimer's disease; Analytical Chemistry; Biochemical Engineering; Biochemistry; Biomedical and Life Sciences; Blood; blood serum; Brain; Cerebrospinal fluid; Chromatography; cognition; Cognitive ability; Dementia disorders; females; Frontal gyrus; Glutamatergic transmission; Glutamic acid; Glutamine; Glycine; High-performance liquid chromatography; Life Sciences; males; Neurobiology; Neurodegenerative diseases; Neurotransmission; Original Article; protein content; Proteomics; synaptic transmission; Tau protein; Alzheimer’s disease; Glutamate; Mild cognitive impairment; Glutamine; Dementia; L-Glutamine; L-Glutamate
• ISSN: 0939-4451; 1438-2199; 1438-2199
• DOI: 10.1007/s00726-021-02943-7

Altered glutamatergic neurotransmission is thought to play a crucial role in the progression of Alzheimer’s disease (AD). Accordingly, the identification of peculiar biochemical patterns reflecting AD-related synaptopathy in blood and cerebrospinal fluid (CSF) could have relevant diagnostic and prognostic implications. In this study, we measured by High-Performance Liquid Chromatography the amount of glutamate, glutamine and glycine in post-mortem brain samples of AD patients, as well as in CSF and blood serum of drug-free subjects encompassing the whole AD clinical spectrum (pre-clinical AD, n  = 18, mild cognitive impairment-AD, n  = 29, dementia AD, n  = 30). Interestingly, we found that glutamate and glycine levels, as well as total tau protein content, were significantly reduced in the superior frontal gyrus of patients with AD, compared with non-demented controls. No significant change was also found in glutamate, glutamine and glycine CSF concentrations between AD patients and neurological controls. Remarkably, serum glutamate levels were significantly higher in patients affected by early AD phases compared to controls, and were negatively correlated with CSF total tau levels. Conversely, serum glutamine concentration was significantly increased in AD patients, with a negative correlation with MMSE performances. Finally, we reported a significant correlation between serum  l -glutamate concentrations and CDR score in female but not in male cohort of AD subjects. Overall, our results suggest that serum glutamate and glutamine levels in AD patients could vary across disease stages, potentially reflecting the progressive alteration of glutamatergic signaling during neurodegenerative processes.