Abstract TP238: Blood Brain Barrier Injury Detected in the Serum of Patients With a History of Stroke and Transient Ischemic Attack

Abstract

Introduction: Stroke and transient ischemic attack (TIA) increase risk for cognitive impairment and dementia. Without a lasting infarction, the cause of cognitive decline after TIA remains unknown. We hypothesize that these cerebrovascular accidents (CVAs) have long-term negative effects on the blood brain barrier (BBB) and promote endothelial inflammation, both of which are associated with neurodegeneration. We sought to investigate the effects of CVAs on BBB integrity and endothelial inflammation by evaluating PDGFRβ and VCAM-1 serum levels, respectively. Methods: A subset of 88 subjects in the Arizona Study of Aging and Neurodegenerative Disorders with postmortem serum samples were available for analysis. Sandwich ELISA was performed to detect PDGFRβ and VCAM-1. Statistical analyses were performed using Spearman’s rank correlation and Mann Whitney U test. Results: Our subjects were split based on CVA status and matched according to vascular risk factors. Both subjects with stroke and subjects with TIA had increased serum PDGFRβ compared to those without history of CVA (6608.4 pg/mL and 5337.0 pg/mL, P=0.04, and 7849.5 pg/mL vs. 5337.0 pg/mL, P<0.01). No significant differences related to PDGFRβ were observed between subjects with stroke vs. TIA (P=0.25). PDGFRβ was associated with VCAM-1 (Spearman’s r=0.44, P<0.01) and VCAM-1 trends towards being higher in subjects with CVA compared to those without (P=0.13). Conclusions: PDGFRβ was elevated in subjects who had a history of stroke or TIA compared to matched patients without CVA. These data demonstrate the utility of a serum-based biomarker of BBB integrity, a powerful tool in studying the role of the BBB in various neurodegenerative diseases including Alzheimer’s dementia. These data also raise the possibility that TIA and stroke have lasting effects on BBB integrity and provide insight about their mechanistic role in neurodegeneration. These findings are limited by our small sample size and post-mortem serum collection; still more, these promising serum biomarkers need further validation.