Investigation of 91 proteins implicated in neurobiological processes identifies multiple candidate plasma biomarkers of stroke outcome

Abstract

The inter-individual variation in stroke outcomes is large and protein studies could point to potential underlying biological mechanisms. We measured plasma levels of 91 neurobiological proteins in 209 cases included in the Sahlgrenska Academy Study on Ischemic Stroke using a Proximity Extension Assay, and blood was sampled in the acute phase and at 3-month and 7-year follow-ups. Levels were also determined once in 209 controls. Acute stroke severity and neurological outcome were evaluated by the National Institutes of Health Stroke Scale. In linear regression models corrected for age, sex, and sampling day, acute phase levels of 37 proteins were associated with acute stroke severity, and 47 with 3-month and/or 7-year outcome at false discovery rate < 0.05. Three-month levels of 8 proteins were associated with 7-year outcome, of which the associations for BCAN and Nr-CAM were independent also of acute stroke severity. Most proteins followed a trajectory with lower levels in the acute phase compared to the 3-month follow-up and the control sampling point. Conclusively, we identified multiple candidate plasma biomarkers of stroke severity and neurological outcome meriting further investigation. This study adds novel information, as most of the reported proteins have not been previously investigated in a stroke cohort.