Objective: To evaluate plasma and PBMC biomarkers of neurodegeneration, neuroinflammation, microglial activation, and oxidative stress across clinically defined stages of Parkinson’s disease (PD).
Background: PD is driven by progressive neurodegeneration in which neuroinflammation and oxidative stress play central roles. Whether neurofilament light chain (NfL), TREM2, and antioxidant enzymes become dysregulated concurrently or follow distinct stage-dependent trajectories remains unclear. Delineating these patterns could reveal stage-specific therapeutic targets and improve disease monitoring.
Method: Sixty-three age- and sex-matched participants were enrolled: PD de novo (n=14), PD intermediate (n=21), PD advanced (n=14), and healthy controls (HC, n=14), classified according to disease duration and Hoehn & Yahr stage. Plasma levels of NfL, fractalkine, IFN-γ, IL-1β, TNF-α, IL-6, and TREM2 were measured using the Ella platform, while Nrf2, SOD1, and HO1 were assessed in PBMCs by Western blot.
Results: TREM2 was significantly reduced in PD de novo and PD intermediate vs. HC (p=0.0226; p=0.0328). SOD1 was similarly reduced in both early groups (p=0.0428; p=0.0306). NfL was elevated in PD intermediate and PD advanced vs. HC (p=0.0370; p=0.0208), and higher in PD advanced than PD de novo (p=0.0408). No significant differences were found for fractalkine, IFN-γ, IL-1β, TNF-α, IL-6, Nrf2 or HO1.
Conclusion: To our knowledge, this is among the first studies to simultaneously profile microglial activity (TREM2), antioxidant defense (SOD1), and axonal injury (NfL) across defined PD stages. The divergent temporal trajectories of these biomarkers, with TREM2 and SOD1 declining early while NfL rises progressively, suggest a staged sequence in which impaired microglial function and antioxidant capacity may precede overt neurodegeneration. Confirmation in larger longitudinal cohorts is needed to establish clinical utility for staging and therapeutic stratification.
To cite this abstract in AMA style:
A. Calculli, D. Di Martino, R. Stiuso, H. Ferrari, C. Fazio, D. Comolli, P. Grillo, N. Polverino, M. Mancini, A. Pisani. Stage-Dependent Dysregulation of Peripheral TREM2, SOD1, and Neurofilament Light Chain Across the Parkinson’s Disease Continuum [abstract]. Mov Disord. 2026; 41 (suppl 1). https://www.mdsabstracts.org/abstract/stage-dependent-dysregulation-of-peripheral-trem2-sod1-and-neurofilament-light-chain-across-the-parkinsons-disease-continuum/. Accessed October 1, 2026.« Back to 2026 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/stage-dependent-dysregulation-of-peripheral-trem2-sod1-and-neurofilament-light-chain-across-the-parkinsons-disease-continuum/