Blood test proteins predict stroke risk better than current clinical tools
Researchers identified a set of blood proteins that forecast future brain strokes and bleeds more accurately than existing risk scores. The discovery opens a path to new diagnostic tests and drugs targeting the root cause of small-vessel disease, a major driver of stroke and cognitive decline affecting millions worldwide.
Originaltitel: Identification of distinct and shared biomarker panels in different manifestations of cerebral small-vessel disease through proteomic profiling
The pathophysiology underlying various manifestations of cerebral small-vessel disease (cSVD) remains poorly understood. Using high-throughput proteomics, we identified common and distinct proteomic signatures of white matter lesions (WMLs), microbleeds, infarcts and their subtypes, measured in 1,670 living patients. Across all cSVD manifestations, markers of extracellular matrix dysregulation and vascular remodeling were increased, including ELN, POSTN, CCN2 and especially MMP12, implicating endothelial and smooth muscle cells of the brain. These proteins were validated in cerebrospinal fluid from two additional datasets, and a subset detected in plasma predicted future cerebrovascular events in the UK Biobank better than risk scores currently used in clinical practice. Analysis focusing on WMLs found microglial-associated proteins associated with faster WML progression, whereas specific neuron-derived proteins mediated the link between WMLs and longitudinal cognitive decline. These data provide a comprehensive atlas of cSVD biomarkers, and our findings provide a promising roadmap for future diagnostics and therapeutics.