Objective: As Parkinson’s disease progresses, patients require second-line treatments such as subthalamic stimulation, the benefits of which may be undermined by the appearance of non-dopaminergic axial motor and cognitive disorders. Our aim is to identify blood biomarkers of ferroptosis, which could predict the severity and cognitive decline of parkinsonian patients at a stage of L-dopa complications.
Background: There is no predictive biomarkers for Parkinson’s disease (PD) progression and severity making difficult the effective stratification of patients in clinical trials. Currently, number of studies attempt to correlate the levels of tau/alpha-synuclein/cytokine protein/NfL in the plasma and the cerebrospinal fluid of PD patients to the severity of motor and cognitive progressions. However, although ferroptosis is now considered as a major mechanism underlying dopaminergic neuronal death, the role of ferroptotic biomarkers towards PD progression has never been investigated.
Method: We analyzed 598 blood samples of PD patients, candidate to subthalamic stimulation. NfL, 4-hydroxy-2-nonenal, glutathione peroxidase activity, ferritin, alpha-synuclein and selenium were measured using electrochemiluminescence, ELISA or inductively coupled plasma mass spectrometry. We assessed three single nucleotide polymorphisms associated with variations of ACSL4 and GPX4 mRNAs, two key players of ferroptosis. Overall clinical outcomes were evaluated at the baseline and one-year post-surgery.
Results: At baseline, UPDRS-III-Worst OFF was positively correlated with 4-HNE (p=0.012) and alpha-synuclein (p=0.016); PDQ-39 was negatively correlated with selenium (p=0.026), ferritin (p=0.010), and haplotype of ACSL4 gene which had statistical interaction with selenium (p=0.003). The polymorphism rs139736475 in ACSL4 gene was correlated with less cognitive disorders (p=0.032). One-year post-surgery, PDQ-39 was negatively correlated with ferritin (p=0.017) and both SNPs in ACSL4 gene were correlated with a preservation of cognitive function (p=0.031 and p=0.022).
Conclusion: Our results indicate that blood-based ferroptotic biomarkers could predict the severity and cognitive decline of Parkinson’s disease. Subject to further validation, they could therefore be used to select and stratify the patients in future clinical trials.
To cite this abstract in AMA style:
V. Huin, E. Cailliau, G. Garçon, M. Dutheil, O. Simonin, N. Beauval, J. Labreuche, D. Blum, C. Moreau, E. Hainque, A. Marques, A. Eusebio, I. Benatru, C. Brefel-Courbon, D. Maltete, C. Giordana, M. Tir, S. Thobois, JP. Brandel, B. Jarraya, L. Hopes, O. Rascol, JC. Corvol, D. Devos, AS. Rolland. Predicting Parkinson’s disease severity and cognitive decline using blood-based ferroptotic biomarkers [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/predicting-parkinsons-disease-severity-and-cognitive-decline-using-blood-based-ferroptotic-biomarkers/. Accessed October 5, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/predicting-parkinsons-disease-severity-and-cognitive-decline-using-blood-based-ferroptotic-biomarkers/