Citations 1
Brain-derived extracellular vesicle microRNAs in Lewy body and Alzheimer’s disease
Yang, Stephanie , Lin, Andrew A. , Shen, Hanfei , Pappalardo, Laura W., Spychalski, Griffin B. , Forsberg, Leah K. , Grant, Kiera M., Savica, Rodolfo , Reichard, R. Ross , McLean, Pamela J. , Yang, Stephanie J , Jones, David T , Dickson, Dennis W , Reichard, R Ross , Nguyen, Aivi T , Boeve, Brad , McLean, Pamela J , Rosario, Jean G. , Forsberg, Leah K., Grant, Kiera M., Buser, Joshua R. , O’Bryant, Sid, Jones, David T., Dickson, Dennis W. , Nguyen, Aivi T. , Meaney, David F. , Boeve, Bradley F. , Issadore, David
No container title available | June 9, 2025 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract INTRODUCTION Robust plasma-based biomarkers to distinguish Lewy body disease (LBD) and Alzheimer’s disease (AD) are currently lacking. We applied track-etch magnetic nanopore (TENPO) sorting for enrichment of brain-derived extracellular vesicle (EV) signatures as potential biomarkers to address this gap. METHODS We analyzed plasma from 137 autopsy-confirmed patients [30 LBD, 31 AD, 30 AD/LBD, 19 AD with amygdala Lewy bodies (AD/ALB), and 27 controls], sequencing miRNAs from TENPO-isolated GluR2-positive (neuron-enriched) and GLAST-positive (astrocyte-enriched) EVs, and measuring plasma proteins (Aβ40, Aβ42, tau, p-Tau181, p-Tau231) via SIMOA. RESULTS We identified 16 GluR2+, 8 GLAST+, and 4 protein biomarkers with differential expression (false discovery rate-corrected P value < .1) between LBD and AD. A multimodal 15-feature panel classified LBD versus AD with 10-fold cross-validated accuracy = 0.95 and area under the curve (AUC) = 0.96. DISCUSSION Brain-derived EVs offer accurate and accessible miRNA biomarkers for the differential diagnosis of LBD and AD.