Objective: To evaluate the longitudinal systemic transcriptomic profile of neutrophil-related pathways and the pathological infiltration of neutrophil extracellular traps (NETs) into the central nervous system (CNS) in Parkinson’s disease (PD).
Background: While altered neutrophil counts are reported in PD, the specific contribution of NETosisa specialized cell death process that releases DNA-protein complexes—to disease progression remains poorly defined.
Method: Longitudinal transcriptomics: We analyzed whole-blood RNA-sequencing data from the Parkinson’s Progression Markers Initiative (PPMI) cohort, comparing baseline and 36-month follow-up samples.
Systemic biomarker analysis: Serum NET formation was quantified via myeloperoxidase (MPO)-DNA complexes using ELISA in an independent regional cross-sectional cohort to assess clinical correlations.
Neuropathology: NET structures in post-mortem brain tissues from individuals with PD, Multiple System Atrophy (MSA), and healthy controls were quantified by ELISA and visualized using high-resolution confocal microscopy.
Results: Systemic Priming: Transcriptomic analysis revealed a persistent, significant upregulation of PADI4 (the key enzyme for NET-priming) in PD patients compared to controls at baseline, which was sustained throughout the 36-month follow-up period.
Circulatory reduction: Paradoxically, serum MPO-DNA complexes were significantly reduced in PD patients and showed a negative correlation with disease severity (MDS-UPDRS).
CNS deposition: In contrast to the serum findings, NET structures were markedly enriched within the CNS of both PD and MSA post-mortem brains. Confocal imaging confirmed extensive infiltration of NET complexes in the midbrain.
Conclusion: Our findings demonstrate a “systemic priming yet central deposition” pattern. The persistent peripheral upregulation of NET-associated pathways (PADI4), coupled with reduced circulating complexes and high CNS deposition, suggests that primed neutrophils may migrate and release NETs within the brain parenchyma. This identifies NETosis as a potential target for immunomodulatory therapy in synucleinopathies.
To cite this abstract in AMA style:
HD. Nguyen, S. Lee, H. Ma, YJ. Kim, HJ. Kim, YE. Kim. The “Sequestration” hypothesis: Longitudinal systemic priming and CNS infiltration of Neutrophil Extracellular Traps in Parkinson’s Disease [abstract]. Mov Disord. 2026; 41 (suppl 1). https://www.mdsabstracts.org/abstract/the-sequestration-hypothesis-longitudinal-systemic-priming-and-cns-infiltration-of-neutrophil-extracellular-traps-in-parkinsons-disease/. Accessed October 1, 2026.« Back to 2026 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/the-sequestration-hypothesis-longitudinal-systemic-priming-and-cns-infiltration-of-neutrophil-extracellular-traps-in-parkinsons-disease/