Enrichment of extracellular vesicles using Mag-Net for the analysis of the plasma proteome.

Journal: Nature communications
Published Date: Jul 1, 2025

Abstract

Extracellular vesicles (EVs) in plasma are composed of exosomes, microvesicles, and apoptotic bodies. We report a plasma EV enrichment strategy using magnetic beads called Mag-Net. Proteomic interrogation of this plasma EV fraction enables the detection of proteins that are beyond the dynamic range of liquid chromatography-mass spectrometry of unfractionated plasma. Mag-Net is robust, reproducible, inexpensive, and requires <100 μL plasma input. Coupled to data-independent mass spectrometry, we demonstrate the measurement of >37,000 peptides from >4,000 proteins. Using Mag-Net on a pilot cohort of patients with neurodegenerative disease and healthy controls, we find 204 proteins that differentiate (q-value < 0.05) patients with Alzheimer's disease dementia (ADD) from those without ADD. There are also 310 proteins that differ between individuals with Parkinson's disease and without. Using machine learning we distinguish between individuals with ADD and not ADD with an area under the receiver operating characteristic curve (AUROC) = 0.98 ± 0.06.

Authors

  • Christine C Wu
    Department of Genome Sciences, University of Washington, Seattle, WA, USA.
  • Kristine A Tsantilas
    Department of Genome Sciences, University of Washington, Seattle, WA, USA.
  • Jea Park
    Department of Genome Sciences, University of Washington, Seattle, WA, USA.
  • Deanna Plubell
    Department of Genome Sciences, University of Washington, Seattle, WA, USA.
  • Justin A Sanders
    Department of Computer Science, University of Washington, Seattle, WA, USA.
  • Previn Naicker
    CSIR, Pretoria, South Africa.
  • Ireshyn Govender
    ReSyn Biosciences, Gauteng, South Africa.
  • Sindisiwe Buthelezi
    CSIR, Pretoria, South Africa.
  • Stoyan Stoychev
    ReSyn Biosciences, Gauteng, South Africa.
  • Justin Jordaan
    ReSyn Biosciences, Gauteng, South Africa.
  • Gennifer Merrihew
    Department of Computer Science, University of Washington, Seattle, WA, USA.
  • Eric Huang
    Department of Genome Sciences, University of Washington, Seattle, WA, USA.
  • Edward D Parker
    Vision Core Lab, Department of Ophthalmology, University of Washington, Seattle, WA, USA.
  • Michael Riffle
    Department of Genome Sciences, University of Washington, Seattle, WA, USA.
  • Andrew N Hoofnagle
    Department of Laboratory Medicine, University of Washington, Seattle, WA.
  • William S Noble
    Department of Genome Sciences, University of Washington , Seattle 98195, Washington, United States.
  • Kathleen L Poston
    From the Departments of Radiology (K.T.C., F.B.d.C.M., S.S., G.Z.), Electrical Engineering (E.G., J.M.P.), and Neurology and Neurological Sciences (A.B., K.L.P., S.J.S., M.D.G., E.M.), Stanford University, 1201 Welch Rd, Stanford, CA 94305; Department of Engineering Physics, Tsinghua University, Beijing, PR China (J.X.); GE Healthcare, Menlo Park, Calif (M.K.); and Subtle Medical, Menlo Park, CA (E.G.).
  • Thomas J Montine
    Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Michael J MacCoss
    Department of Genome Sciences, University of Washington, Seattle, WA, USA.

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