Brain-derived extracellular vesicle microRNAs in Lewy body and Alzheimer's disease

Stephanie J. Yang; Andrew A. Lin; Hanfei Shen; Laura W. Pappalardo; Griffin B. Spychalski; Jean G. Rosario; Leah K. Forsberg; Kiera M. Grant; Joshua R. Buser; Rodolfo Savica; Sid O’Bryant; David T. Jones; Dennis W. Dickson; Robert Ross Reichard; Aivi T. Nguyen; David F. Meaney; Bradley F. Boeve; Owen A. Ross; Pamela J. McLean; David Issadore

doi:10.1038/s44328-026-00086-x

Bioengineeringnpj BiosensingMar 12, 2026

Peer-reviewed journal article

Brain-derived extracellular vesicle microRNAs in Lewy body and Alzheimer's disease

Stephanie J. Yang iD, Andrew A. Lin iD, Hanfei Shen iD, Laura W. Pappalardo, Griffin B. Spychalski iD, Jean G. Rosario iD, Leah K. Forsberg iD, Kiera M. Grant, Joshua R. Buser iD, Rodolfo Savica iD, Sid O’Bryant, David T. Jones, Dennis W. Dickson iD, Robert Ross Reichard iD, Aivi T. Nguyen iD, David F. Meaney iD, Bradley F. Boeve iD, Owen A. Ross iD, Pamela J. McLean iD, David Issadore iD

Abstract

INTRODUCTIONRobust plasma-based biomarkers to distinguish Lewy body disease (LBD) and Alzheimers 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. METHODSWe 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 (A{beta}40, A{beta}42, tau, p-Tau181, p-Tau231) via SIMOA. RESULTSWe 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. DISCUSSIONBrain-derived EVs offer accurate and accessible miRNA biomarkers for the differential diagnosis of LBD and AD.

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