Using proteomic biomarkers to estimate acute ischaemic stroke onset time

Area of Science:

• Biomarker discovery in neurology
• Proteomics and mass spectrometry applications
• Acute ischemic stroke (AIS) research

Background:

• Intravenous thrombolysis (IVT) is recommended for AIS within 4.5 hours of symptom onset.
• Accurate stroke onset time is critical for effective treatment, but often unclear.
• Need for reliable methods to determine stroke onset in uncertain cases.

Purpose of the Study:

• To identify proteomic biomarkers for distinguishing early-onset AIS (≤4.5 h) from late-onset AIS (4.5-24 h).
• To develop a proteomic signature for estimating stroke onset time in patients with unknown history.
• To improve eligibility for timely IVT in AIS patients.

Main Methods:

• Retrospective case-control study involving 30 AIS patients and 12 controls.
• Plasma proteome analysis using mass spectrometry.
• Statistical analysis including stepwise screening and multiple logistic regression to identify candidate proteins and combinations.

Main Results:

• Six proteins were identified that effectively discriminate between early-onset and late-onset AIS (AUC 0.897-0.951).
• Protein 4.2 (EPB42) showed high diagnostic performance (AUC 0.951).
• A combination of EPB42 and Phosphatidylethanolamine-binding protein 1 achieved an AUC of 0.991, with high sensitivity and specificity.

Conclusions:

• Identified proteins and their combinations show potential as 'molecular clocks' for AIS onset time determination.
• These biomarkers could aid in identifying patients eligible for IVT when symptom onset is unknown.
• Improved identification of treatment windows can enhance stroke outcomes.