Association between functional connectome features and circulating amino acid levels in early-stage Parkinson's disease: An exploratory study

Parkinson's disease (PD) is characterized by early alterations in large-scale brain functional connectivity and possible disturbances in excitatory amino acid metabolism. However, it is unknown whether topological changes in functional connectome reflect disruptions in the homeostasis of circulating glutamate and aspartate levels. Resting-state fMRI and High-Performance Liquid Chromatography are used to correlate brain and blood measures in 74 early-stage PD patients (mean age ± s.d. 63.5 ± 8.6 years, 51 males, 37 drug-naïve) and 20 healthy control (HC) volunteers (mean age ± s.d. 60.2 ± 5.6, 11 males). PD-relevant graph-theoretical metrics of fMRI connectomes are co-varied to serum-levels of N-Methyl-d-aspartate receptor (NMDAR)-related (L-/D-) amino acids (including precursors and related ratios). In male PD patients, compared to sex-matched HC subjects, strength of cortical sensorimotor nodes and clustering of subcortical nodes negatively correlate to D-/total aspartate ratio; clustering of temporal nodes positively correlates to l-aspartate; global characteristic path length negatively correlates to L-glutamate. Enlarging the panel of L-amino acids, l-serine markedly predicts metrics in treated male PD patients. Peripheral balance of excitatory amino acids and their precursors appear linked to large-scale brain network (re)organization in early-stage PD, supporting the potential value of these neuroactive biomolecules as circulating markers of functional brain integrity.