Energetic dysfunction and iron overload in early Parkinson's disease: Two distinct mechanisms?

Stephan Grimaldi, Arnaud Le Troter, Mohamed Mounir El Mendili, Hugo Dary, Jean Philippe Azulay, Wafaa Zaaraoui, Jean Philippe Ranjeva, Alexandre Eusebio, Ludovic de Rochefort, Maxime Guye

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: Identifying biomarkers reflecting cellular dysfunctions in early Parkinson's disease patients (ePD) is needed to develop targeted therapeutic strategies. We aimed to determine if cellular energetic dysfunction related to increased brain sodium concentration would be co-located to microstructural alterations and iron deposition in ePD. Methods: We prospectively included 12 ePD (mean disease duration 20.0 ± 10.2 months) and 13 healthy controls (HC), scanned with a 7 T 1H and 23Na MRI. Complementary voxel-based and region-based assessments were performed, the latter utilizing a high-resolution multimodal template we created (combining quantitative T1 maps (qT1), transverse relaxation rate (R2*), quantitative magnetic susceptibility mapping (QSM) images) from 200 subjects. This template allowed a precise multiparametric assessment of sodium concentration, QSM, R2*, qT1, mean diffusivity, and fractional anisotropy values. A two-sided p-value<0.05 was considered statistically significant after the Bonferroni correction. Results: Relative to HC, ePD showed significantly higher sodium concentration in left Substantia nigra (SN) pars reticulata (46.13 mM ± 3.52 vs 38.60 mM ± 6.10, p = 0.038), a subpart of the SN pars compacta (SNc) and ventral tegmental area, Putamen, Globus Pallidum external, accumbens nucleus and claustrum. Significantly increased QSM and R2* values, and decreased T1 values, were limited to the Nigrosomes 1 (Nig) and right SNc (all p < 0.05). QSM values in the Nig were significantly correlated to UPDRS-III scores (r = 0.91,p < 0.001). Conclusion: In ePD, brain sodium accumulation was broad and dissociated from iron accumulation. As with iron accumulation, a sodium-related pathophysiological approach could lead to identifying potential new therapeutic agents and deserves further investigation.

Original languageEnglish
Article number106996
JournalParkinsonism and Related Disorders
Volume124
DOIs
StatePublished - Jul 2024
Externally publishedYes

Keywords

  • Biomarkers
  • Multiparametric magnetic resonance imaging
  • Parkinson disease
  • sodium
  • Synucleinopathies

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