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. 2024 Dec;39(12):2211-2219.
doi: 10.1002/mds.30009. Epub 2024 Sep 16.

Immunometabolic Signature and Tauopathy Markers in Blood Cells of Progressive Supranuclear Palsy

Marco Rosina  1   2 , Federica Veltri  3 , Valentina Nesci  2   3 , Jacopo Bissacco  3 , Roberta Bovenzi  3 , Davide Mascioli  3 , Clara Simonetta  3 , Henri Zenuni  3 , Daniela Maftei  3 , Massimo Marano  4   5 , Mariangela Pierantozzi  1   3 , Alessandro Stefani  1   3 , Valerio Chiurchiù  6   7 , Patrizia Longone  2 , Cristiana Valle  2   6 , Nicola Biagio Mercuri  1   3 , Alberto Ferri  2   6 , Tommaso Schirinzi  1   3
Affiliations

Immunometabolic Signature and Tauopathy Markers in Blood Cells of Progressive Supranuclear Palsy

Marco Rosina et al. Mov Disord. 2024 Dec.

Abstract

Background: Peripheral immune cells critically contribute to the clinical-pathological progression of neurodegenerative diseases and also represent a reliable frame for translational applications. However, data on progressive supranuclear palsy (PSP) are almost scarce in this regard.

Objective: Our goal is to provide a broad biological characterization of peripheral immune cells in a selected PSP cohort.

Methods: Seventy-one PSP patients scored on the PSP Rating Scale (PSPRS), and 59 controls were enrolled. The blood cell count was collected, together with the neutrophil-to-lymphocyte ratio (NLR) calculation. In a subgroup of patients and controls, the peripheral blood mononuclear cells (PBMCs) were analyzed by the mitochondrial bioenergetic performance and the western blot assay of the nuclear factor erythroid 2-related factor (NRF2)/heme oxygenase 1 (HO-1) pathway and the total tau (t-tau) and phosphorylated tau (p-tau) proteins. Case-control comparison and correlation analyses were performed.

Results: PSP patients had a NLR higher than controls, with increased circulating neutrophils. The leukocyte metabolism was also globally increased and the NRF2/HO-1 pathway activated in patients. P-tau, but not t-tau, significantly accumulated in PSP PBMCs and inversely correlated with the PSPRS.

Conclusions: PSP displays a systemic inflammatory shift of the peripheral immunity, which may justify a metabolic reprogramming of the blood leukocytes. Consistently, the NRF2/HO-1 pathway, a master regulator of inflammatory and metabolic response, was activated. PBMCs also engulf tau proteins, especially p-tau, in a way inverse to the disease severity, allowing for a peripheral tracking of tauopathy in patients. Immunometabolic targets may, therefore, gain relevance to PSP in biomarker or therapeutic purposes. © 2024 International Parkinson and Movement Disorder Society.

Keywords: PBMC; PSP; Progressive Supranuclear Palsy; TAU; biomarkers; immunometabolism; neutrophil‐to‐lymphocyte ratio.

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