Ultra-performance liquid chromatography-mass spectrometry analysis of post-mortem brain tissue reveals specific amino acid profile dysregulation in Parkinson's disease and Alzheimer's disease patients.
Ultra-performance liquid chromatography-mass spectrometry analysis of post-mortem brain tissue reveals specific amino acid profile dysregulation in Parkinson's disease and Alzheimer's disease patients.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Rome, IT · Author affiliation
Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli 8, Roma, Italy.Location evidence
Naples, IT · Author affiliation
CEINGE Biotecnologie Avanzate Franco Salvatore, Naples, Italy.Location evidence
Caserta, IT · Author affiliation
Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Università degli Studi della Campania "Luigi Vanvitelli", Caserta, Italy.Location evidence
Cagliari, IT · Author affiliation
Department of Biomedical Sciences, University of Cagliari, Monserrato, Italy.Location evidence
Monserrato, IT · Author affiliation
Department of Biomedical Sciences, University of Cagliari, Monserrato, Italy.Location evidence
Cattolica, IT · Author affiliation
Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, Roma, Italy.Location evidence
Floirac, FR · Author affiliation
Motac France, Floirac, France.Location evidence
Bordeaux, FR · Author affiliation
Université de Bordeaux, CNRS, IMN, UMR 5293, Bordeaux, France.Location evidence
Portici, IT · Author affiliation
Department of Agricultural Sciences, University of Naples "Federico II", Portici, Italy.Location evidence
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Original abstract
Previous metabolomic studies have reported significant alterations in circulating amino acids in Parkinson's disease (PD). However, it remains unclear whether these changes reflect central nervous system pathology or are restricted to peripheral metabolism. To address this issue, here we measured the levels of a panel of amino acids in post-mortem brain samples from MPTP-intoxicated monkeys, with and without L-DOPA treatment, and from PD patients at different Braak Lewy body (LB) stages through targeted UPLC-MS. In untreated MPTP monkeys, the putamen showed significant increases in glutamate, aspartate, GABA, phenylalanine, branched-chain amino acids, and serine. L-DOPA treatment further altered this profile, increasing glycine, threonine, and citrulline levels. In contrast, no amino acid changes were detected in the superior frontal gyrus (SFG) of MPTP monkeys, regardless of treatment. In PD patients, caudate-putamen analysis revealed consistent serine upregulation at Braak LB stages 3-4 and 6, with stage 6 additionally showing increased proline and reduced phosphoethanolamine. No amino acid changes were observed in the PD SFG, whereas Alzheimer's disease SFG samples showed marked amino acid increases. Together, these findings demonstrate region-specific amino acid dysregulation in PD, preferentially affecting nigrostriatal targets and supporting disease-specific metabolic signatures across neurodegenerative disorders.