Soluble Urokinase-type Plasminogen Activator Receptor (suPAR) as a Biomarker of Neurodysfunction

TL;DR

This review explores how suPAR, a marker of chronic inflammation, may be linked to brain dysfunction and neuroinflammation.

Contribution

The paper highlights suPAR's emerging role as a biomarker connecting systemic inflammation to central nervous system dysfunction.

Findings

Higher suPAR levels are associated with memory impairment and poor outcomes after brain injury.

suPAR reflects neuroinflammation and blood-brain barrier disruption in immune-activated conditions.

Study designs and populations vary, limiting clear mechanistic understanding of suPAR's role in the CNS.

Abstract

The inflammatory response is essential for host defense, but its persistence can lead to chronic systemic inflammation (CSI). Soluble urokinase-type plasminogen activator receptor (suPAR) has emerged as a reliable biomarker of CSI because elevated levels consistently indicate the presence and progression of chronic disease as well as increased mortality risk. There is growing evidence that CSI influences neurovascular regulation, including changes in blood-brain barrier (BBB) integrity, which suggests that suPAR may also be relevant to central nervous system (CNS) processes. This narrative review summarizes current findings on suPAR in CSI and examines its emerging implications for CNS. Higher suPAR concentrations have been linked to working memory impairment, executive dysfunction and worse clinical outcomes after brain injury. Evidence also indicates that suPAR reflects neuroinflammatory activity and BBB disruption, especially in conditions marked by heightened immune activation. However, available studies differ widely in design, sample type, follow-up duration and population characteristics, which limits mechanistic interpretation. Although suPAR appears to be a promising biomarker connecting systemic inflammation to CNS dysfunction, its role within the brain remains unclear. Future studies should determine its cellular origin, clarify its involvement in inflammatory signaling pathways and establish its predictive and prognostic value.

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