Microfluidic nanomagnetically isolated neuron- and astrocyte-derived extracellular vesicles to differentiate Lewy body and Alzheimer’s disease
Identifying plasma-based biomarkers that can accurately differentiate Lewy body disease (LBD) from Alzheimer's disease (AD) remains a major challenge. Extracellular vesicles (EVs), which carry molecular cargo from their parent cells and can cross the blood-brain barrier, offer a new path forward. We developed the multiplexed Track-Etch magnetic NanoPOre (mTENPO) platform, a highly parallelized microfluidic technology for cell-specific EV isolation, and demonstrated independent enrichment of GluR2+ (neuron-derived) and GLAST+ (astrocyte-derived) EVs from the antemortem plasma of 137 autopsy-confirmed LBD, AD, mixed pathology, and control subjects. By integrating miRNA sequencing of GluR2+ and GLAST + EV cargo with plasma measurements of Aβ40, Aβ42, tau, p-Tau181, and p-Tau231, we identified a multimodal 15-feature panel that more comprehensively reflects brain pathology than conventional biomarkers. Using tenfold cross-validation to mitigate overfitting, the panel achieved an accuracy of 0.95 and an area under the curve of 0.96 for distinguishing LBD versus AD.
Authors
- Pamela J. McLean (ORCID: https://orcid.org/0000-0003-4870-5715)
- Joshua R. Buser (ORCID: https://orcid.org/0000-0003-3555-8154)
- Griffin B. Spychalski (ORCID: https://orcid.org/0000-0002-7210-6416)
- Laura W. Pappalardo
- Hanfei Shen (ORCID: https://orcid.org/0000-0002-1804-5982)
- Aivi T. Nguyen (ORCID: https://orcid.org/0000-0003-1809-9451)
- David Issadore (ORCID: https://orcid.org/0000-0002-5461-8653)
- Jean G. Rosario (ORCID: https://orcid.org/0000-0002-6116-5058)
- David F. Meaney (ORCID: https://orcid.org/0000-0002-0954-4122)
- Owen Ross
- Stephanie Yang (ORCID: https://orcid.org/0000-0002-2465-3896)
- Bradley F. Boeve
- David Cecil Jones
- Kiera M. Grant
- Dennis W. Dickson
- Andrew A. Lin
- Rodolfo Savica
- Leah K. Forsberg
- R. Ross Reichard
- Sid O’Bryant
Institutions
- University of North Texas (US)
- Mayo Clinic (US)
- University of North Texas Health Science Center (US)
- Hospital of the University of Pennsylvania (US)
- WinnMed (US)
- Consol Energy (United States) (US)
- Mayo Clinic in Arizona (US)
- Mayo Clinic in Florida (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- npj Biosensing
- Published
- 2026-03-12
- DOI
- https://doi.org/10.1038/s44328-026-00086-x
- Primary Topic
- Extracellular vesicles in disease
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Science Foundation
- American Brain Foundation
- University of Pennsylvania
- Little Family Foundation
- National Institutes of Health
- Perelman School of Medicine, University of Pennsylvania
- Materials Research Science and Engineering Center, Harvard University
- Division of Materials Research