A Novel Blood-Based Biomarker for Silent Cerebral Edema and Brain Vascular Injury

Emerging data from several expansive clinical trials indicates that common chronic vascular risk factors such as diabetes, hypertension, obesity, and age increase the risk of stroke and dementia. This increased risk occurs through direct injury to brain blood vessels resulting from these risk factors and causes brain blood vessel leakage, cerebral edema, and ultimately permanent brain tissue injury. There are currently no clinical biologic assays to directly measure brain blood vessel health. Widely available imaging techniques provide limited quantitative information and only indicate cerebrovascular damage that has already occurred. To develop a blood-based biomarker for early brain vascular injury, we utilized a custom Luminex multiplex assay to measure the serum/plasma levels of six inflammatory molecules in two patient cohorts. In both discovery and validation cohorts (n=298 total), levels of the six defined circulating inflammatory molecules were not only associated with permanent vascular brain injury as measured by T2/FLAIR MRI signal intensity but also with cerebral free water, a diffusion tensor MRI measure of cerebral edema. A population mean-adjusted single composite inflammatory index score resulted in 94% specificity for severe cerebrovascular disease detection. Detection of clinically silent cerebral edema was increased two-fold in subjects with an elevated composite inflammatory index. Circulating cytokines and interleukin molecules present in measurable quantities by high sensitivity multiplex immunoassay can serve as a surrogate biomarker for cerebrovascular disease status that can be utilized to reduce the risk of stroke and dementia.

Learning Objectives:

1. Recognize common chronic vascular risk factors such as diabetes, hypertension, obesity, and age increase the risk of stroke and dementia.

2. Understand how a custom assay multiplexing technology was used in blood based diagnostics for silent brain vascular injury research.