Plasma amino acids patterns and age of onset of amyotrophic lateral sclerosis

Abstract

The aim of this study was to verify whether abnormalities in plasma amino acid (AA) levels could be biological correlates of the age of onset in amyotrophic lateral sclerosis (ALS). We undertook plasma AA profiling in a large population comprising 117 newly diagnosed ALS patients and 117 matched controls. ALS patients were stratified in early (58 patients aged < 55 years) versus late onset (59 patients aged > 74 years). We applied a rapid and reproducible method for the analysis of AA using amine reactive isotope coded tags in conjunction with liquid chromatography coupled to Multiple Reaction Monitoring-Mass Spectrometry. Results showed that values of only three AA were significantly different in ALS patients and controls. We found lower levels of leucine and higher levels of glutamate and leucine in early-onset ALS compared to their matched controls. In conclusion, different AA patterns related to the ALS age of onset were found, providing insight into possibly aberrant biochemical pathways that might unlock key pathological pathways.

Key words::

• Amyotrophic lateral sclerosis
• plasma amino acids
• age at onset
• spectrometry

Acknowledgement

This work was supported by a grant from ‘Genetic and environmental predictors of early onset of Amyotrophic Lateral Sclerosis’.

Declaration of interest: P. Messina has received funding from Sanofi-Aventis, EISAI, Lombardy Region, and the American ALS Association for data analysis and data management of RCT and observational study protocol. E. Pupillo has received funding from the American ALS Association and Italian Ministry of Health for data management and data monitoring of an observational study protocol. She received funding from Italian Drug Agency (AIFA) for data monitoring and study management of randomized clinical trial. J. Mandrioli has received research support from Regione Emilia Romagna (‘Programma di Ricerca Regione- Università 2010–2012, area 2, Ricerca per il Governo Clinico’, and ‘Emilia Romagna Registry for ALS – ERRALS’). E. Beghi has received remuneration for board membership by Viropharma and Eisai; has received funding for travel and speaker honoraria from UCB-Pharma, GSK and for educational presentations from GSK; has received grants for research activities from the Italian Drug Agency, Italian Ministry of Health and the American ALS Association.

The authors alone are responsible for the content and writing of the paper.