Related Experiment Video
Updated: Sep 15, 2025
Harnessing the Power of MicroRNA Cargoes in Small Extracellular Vesicles Released from Fresh-Frozen Human Brain Sections
Published on: November 8, 2024
Brain-derived extracellular vesicle microRNAs in Lewy body and Alzheimer's disease
Stephanie J Yang1, Andrew A Lin1,2, Hanfei Shen1
1Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
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 crossvalidated 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.
