Abstract Body: The ability to differentiate cerebrovascular disease (CVD) with plasma biomarkers could be an invaluable tool. CVD encompasses a spectrum of conditions that alter intracranial blood flow and activate endothelial cells (ECs), which results in a dysregulated blood brain barrier (BBB). Activated ECs upregulate and cleave many junctional proteins, including soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intracellular adhesion molecule-1 (sICAM-1), and von Willebrand factor (vWF). These junctional complexes regulate BBB permeability and infiltration of leukocytes that release interferon-gamma (IFN-gamma) for immune cell regulation. Key barriers to providing therapies for CVD are due to lack of biomarkers to differentiate pathologies. Utilizing extracellular vesicles (EVs), which are nanoparticles, released from all cell carrying cargo specific to their parent cells microenvironment, may provide insight into cerebrovascular changes before overt pathological and cognitive changes are present. Therefore, we unbanked plasma from the Blood And Clot Thrombectomy Registry And Collaboration” (BACTRAC; NCT03153683) and “Moyamoya and Stroke Tissue Evaluation and Repository” (MASTER) to measure EV sVCAM-1, sICAM-1, vWF and IFN-γ concentrations in aneurysms, emergent large vessel occlusions (ELVO), and Moyamoya. Moyamoya vasculopathy is a unique CVD that presents with internal carotid artery terminus stenosis and abnormal vascular collaterals. EVs were isolated using size exclusion chromatography, concentrated, and the protein ran on MSD assays. Aneurysms (n=17, 76.5% female), ELVO (n=20, 65% female), and Moyamoya (n=21, 66.7 % female) did not have significant differences in sex, body mass indexes, hypertension, smoking status or diabetes between groups. ELVOs were significantly older (72.75 ± 3.3 years) than Moyamoya (47.2.1 ±2.0, p<0.0001) and aneurysms (50.9 ± 5.5, p=0.01) and had significantly lower EV IFN-gamma (p=0.004). In ELVOs, lower EV IFN-gamma correlated to larger edema volumes (p=0.023, r=-0.821) and higher stroke severity (NIHSS, r=-0.812, p=0.05). Moyamoya EVs showed increased sVCAM-1 (p= 0.069) and sICAM (p=0.057), compared to aneurysm, with significantly lower (p=0.001) vWF, compared to aneurysms and ELVOs. Higher EV sICAM-1 trended (p=0.059, r=0.794) for better cognitive outcomes following ELVO. These data suggest that markers of BBB dysregulation in plasma EVs could provide some insight into type and severity of CVD.