Abstract WP247: Amylin, A Diabetes-associated Amyloid-forming Peptide, Accumulates In Thrombi And On Red Blood Cells - A New Biomarker For Stroke?

Abstract

Emergent large vessel occlusions result in severe ischemic stroke without appropriate treatment with thrombolysis and/or mechanical thrombectomy. Type-2 diabetes mellitus (T2DM) is a major risk factor in stroke, with 25% of ischemic attacks occurring in individuals with T2DM. T2DM diagnosis is also associated with poorer functional outcomes, prolonged hospitalizations, and increased risk of recurrent stroke. Amylin, a peptide co-secreted with insulin in pancreatic β-cells, is hypersecreted in T2DM and readily forms neurotoxic oligomers which deposit in brain parenchyma. Due to amylin’s role in T2DM and T2DM’s relationship to stroke, we anticipated an increased level of amylin would be deposited on red blood cells (RBCs) of stroke patients when compared to non-stroke patients. Additionally, we anticipated an increased level of amylin immunoreactivity (AIR) in clot lysates when compared to RBC lysates and plasma. Blood samples and thrombi ( n =47) were collected from patients undergoing mechanical thrombectomies for stroke while blood samples ( n =21) were collected from patients with non-stroke neurological conditions. Samples were lysed and assayed for total protein concentration and intensity of AIR. Amylin uptake coefficients (AUCs) demonstrating the proportionality of amylin deposited on RBCs compared to total circulating amylin were calculated. After normalizing to total protein concentration, analysis revealed a significantly increased level of AIR in stroke clots when compared to stroke and non-stroke plasma and RBC lysates (p<0.001 for each). Additionally, a significant increase (p<0.0073) in AUC was found in stroke versus non-stroke. In summary, amylin accumulates in thrombi and deposits on RBCs of stroke patients. Further research into amylin’s potential role in thrombus formation is justified. Future studies are also needed to determine if stroke severity is associated with amylin level in thrombi and if T2DM exacerbates amylin-stroke pathology.