441 Markers of blood–brain barrier impairment and inflammation in CAA-ri

Abstract

Objectives/Goals: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a spontaneous inflammatory cerebral vasculopathy that mimics complications of Alzheimer’s disease immunotherapies. Our objective is to evaluate imaging and cerebrospinal fluid (CSF) markers of blood–brain barrier (BBB) impairment and inflammation in CAA-ri. Methods/Study Population: We plan to enroll 20 patients total: 1) 10 patients with CAA-ri as defined by Auriel et al (JAMA Neurology 2016) (exposure group). 2) 10 patients with non-inflammatory CAA defined using Boston criteria 2.0 that do not also meet criteria for CAA-ri (control group). The primary outcome will be Ktrans, a parameter of BBB impairment calculated from dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) of the brain. Secondary outcomes will include DCE-MRI parameter VL, CSF albumin index, CSF fibrinogen, CSF sPDGFR-β, CSF MMP-2, CSF MMP-9, CSF C3, CSF IL1β, CSF IL6, IL8, and TNFα. Statistical comparisons between the exposure and control groups will be made using Wilcoxon rank sum test. Results/Anticipated Results: We anticipate significantly higher levels of BBB impairment and inflammatory biomarkers from DCE-MRI and CSF in subjects with CAA-ri relative to control subjects with non-inflammatory CAA. Discussion/Significance of Impact: Biomarkers are essential to characterize risk factors, pathophysiology, and possible treatment targets in CAA-ri. We plan to use the results of the current study to inform longitudinal studies that will test whether these markers are useful in identifying not only the presence of CAA-ri but also severity, progression, and response to treatment.