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

1. NPJ Parkinsons Dis. 2026 Mar 4;12(1):95. doi: 10.1038/s41531-026-01306-x.

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.

Gervasoni J(1), Di Maio A(2)(3), Serra M(4), Cicchinelli M(5), Santucci L(1)(5),
Ciasca G(5), Nuzzo T(2)(3), Li Q(6), Thiolat ML(7), Morelli M(4)(8), Urbani
A(1)(5), Errico F(2)(9), Bezard E(6)(7), Usiello A(10)(11).

Author information:
(1)Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli
8, Roma, Italy.
(2)CEINGE Biotecnologie Avanzate Franco Salvatore, Naples, Italy.
(3)Department of Environmental, Biological and Pharmaceutical Sciences and
Technologies, Università degli Studi della Campania « Luigi Vanvitelli », Caserta,
Italy.
(4)Department of Biomedical Sciences, University of Cagliari, Monserrato, Italy.
(5)Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, Roma, Italy.
(6)Motac France, Floirac, France.
(7)Université de Bordeaux, CNRS, IMN, UMR 5293, Bordeaux, France.
(8)Neuroscience Institute, National Research Council of Italy (CNR), Cagliari
Cittadella Universitaria, Monserrato, Italy.
(9)Department of Agricultural Sciences, University of Naples « Federico II »,
Portici, Italy.
(10)CEINGE Biotecnologie Avanzate Franco Salvatore, Naples, Italy.
.
(11)Department of Environmental, Biological and Pharmaceutical Sciences and
Technologies, Università degli Studi della Campania « Luigi Vanvitelli », Caserta,
Italy. .

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.

© 2026. The Author(s).

DOI: 10.1038/s41531-026-01306-x
PMCID: PMC13077096
PMID: 41775741

Conflict of interest statement: Competing interests: The authors declare no
competing interests.

Auteurs Bordeaux Neurocampus