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bioRxiv · 10.1101/2024.12.05.625499

Peripheral immune cell response to stimulation stratifies Parkinson's disease progression from prodromal to clinical stages

Mark, J. R.·Titus, A.·Staley, H. R.·Alvarez, S.·Mahn, S.·McFarland, N.·Tansey, M. G.·Wallings, R.
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Abstract

The motor stage of idiopathic Parkinsons disease (iPD) can be preceded for years by a prodromal stage characterized by non-motor symptoms like REM sleep behavior disorder (RBD). Here, we show that multiple stages of iPD, including the pre-motor prodromal stage, can be stratified according to the inflammatory and immunometabolic responses to stimulation of peripheral blood mononuclear cells ex vivo. We identified increased stimulation-dependent secretion of TNF, IL-1{beta}, and IL-8 in monocytes from RBD patients and showed diminished proinflammatory cytokine secretion in monocytes and T cells in early and moderate stages of PD. Mechanistically, immune activation revealed deficits in CD8+ T-cell mitochondrial health in moderate PD, and relative mitochondrial health in CD8+ T cells was positively correlated with stimulation-dependent T-cell cytokine secretion across the PD spectrum. Dysregulated immunometabolism may drive peripheral inflammation and PD progression, and ex vivo stimulation-based assays have potential to reveal novel biomarkers for patient stratification and progression with immune endophenotypes.

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Mark, J. R., Titus, A., Staley, H. R., Alvarez, S., Mahn, S., McFarland, N., Tansey, M. G., Wallings, R.. 2024-12-07. Peripheral immune cell response to stimulation stratifies Parkinson's disease progression from prodromal to clinical stages. https://doi.org/10.1101/2024.12.05.625499

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