Peripheral immune dysregulation in Parkinson's disease: Integrative analysis of human transcriptomics and preclinical validation
Peripheral immune dysregulation in Parkinson's disease: Integrative analysis of human transcriptomics and preclinical validation
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Original abstract
Parkinson’s Disease (PD) is increasingly recognized as a disorder involving systemic immune dysregulation beyond central dopaminergic neurodegeneration. This research integrates a publicly available single-cell transcriptomic dataset from peripheral blood mononuclear cells (PBMCs) of PD patients with preclinical validation in an α-synuclein-injected mouse model. Transcriptomic analyses revealed altered lymphocyte states in PD, including expansion and activation of cytotoxic CD8⁺ T cell subsets and changes in B cell populations. Differential gene expression highlighted upregulation of cytotoxic markers such as CD8B, GZMA, GZMH, and FGFBP2. Flow cytometry and immunofluorescence analyses of dura mater, spleen, small intestine, and large intestine in the mouse model demonstrated compartment-specific immune alterations, including increased CD8⁺ T cell infiltration. Preliminary findings suggest potential sex-dependent immune differences. These findings support a role for peripheral immune dysregulation in PD pathogenesis and highlight CD8⁺ T cells and meningeal immunity as potential biomarkers and therapeutic targets.