Microfluidic Isolation of Neuronal-Enriched Extracellular Vesicles Shows Distinct and Common Neurological Proteins in Long COVID, HIV Infection and Alzheimer’s Disease

Lynn Pulliam, Bing Sun, Erin McCafferty, Steven A. Soper, Malgorzata A. Witek, Mengjia Hu, Judith M. Ford, Sarah Song, Dimitrios Kapogiannis, Marshall J. Glesby, Daniel Merenstein, Phyllis C. Tien, Heather Freasier, Audrey French, Heather McKay, Monica M. Diaz, Igho Ofotokun, Jordan E. Lake, Joseph B. Margolick, Eun Young KimSteven R. Levine, Margaret A. Fischl, Wei Li, Jeremy Martinson, Norina Tang

Research output: Contribution to journalArticlepeer-review

Abstract

Long COVID (LongC) is associated with a myriad of symptoms including cognitive impairment. We reported at the beginning of the COVID-19 pandemic that neuronal-enriched or L1CAM+ extracellular vesicles (nEVs) from people with LongC contained proteins associated with Alzheimer’s disease (AD). Since that time, a subset of people with prior COVID infection continue to report neurological problems more than three months after infection. Blood markers to better characterize LongC are elusive. To further identify neuronal proteins associated with LongC, we maximized the number of nEVs isolated from plasma by developing a hybrid EV Microfluidic Affinity Purification (EV-MAP) technique. We isolated nEVs from people with LongC and neurological complaints, AD, and HIV infection with mild cognitive impairment. Using the OLINK platform that assesses 384 neurological proteins, we identified 11 significant proteins increased in LongC and 2 decreased (BST1, GGT1). Fourteen proteins were increased in AD and forty proteins associated with HIV cognitive impairment were elevated with one decreased (IVD). One common protein (BST1) was decreased in LongC and increased in HIV. Six proteins (MIF, ENO1, MESD, NUDT5, TNFSF14 and FYB1) were expressed in both LongC and AD and no proteins were common to HIV and AD. This study begins to identify differences and similarities in the neuronal response to LongC versus AD and HIV infection.

Original languageEnglish (US)
Article number3830
JournalInternational journal of molecular sciences
Volume25
Issue number7
DOIs
StatePublished - Apr 2024

Keywords

  • Alzheimer’s disease
  • HIV
  • L1CAM
  • OLINK
  • extracellular vesicles
  • long COVID
  • microfluidics

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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