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<p>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.</p>

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Microfluidic nanomagnetically isolated neuron- and astrocyte-derived extracellular vesicles to differentiate Lewy body and Alzheimer’s disease

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月12日

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

摘要

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.