A roadmap towards clinical use of molecular biomarkers in acute ischaemic stroke

Acute ischaemic stroke remains a leading cause of death and disability worldwide, and even highly effective reperfusion therapies benefit only a fraction of patients. Current clinical decision-making relies largely on clinical examination and imaging, which provide limited insight into the molecular mechanisms that drive injury progression, treatment response and recovery. Molecular biomarkers offer a complementary window into this biology: they can resolve pathway activity at the cellular level, detect pre-morphological tissue stress, report on multi-organ processes and enable high-frequency, minimally invasive monitoring. Here we synthesize emerging evidence across selected, interconnected, outcome-relevant pathomechanisms of acute ischaemic stroke, spanning ischaemic brain injury, metabolism, systemic inflammation and gut dysbiosis. We highlight promising biomarker candidates including brain-derived tau, neurofilament light chain, metabolic and inflammatory signatures and microbiota-derived metabolites and argue that substantial further work is required. In particular, we emphasize the need to prioritize biomarkers as tools for elucidating human stroke pathophysiology rather than focusing solely on therapeutic targets. To guide this effort, we propose a pragmatic, six-phase roadmap from discovery to clinical implementation that emphasizes context of use, assay development, clinical validation and biomarker-guided trials. Applied systematically, mechanism-informed biomarkers could enable more precise, biology-guided stroke care and help to close the translational gap.