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

TitleMicrofluidic Isolation of Neuronal-Enriched Extracellular Vesicles Shows Distinct and Common Neurological Proteins in Long COVID, HIV Infection and Alzheimer's Disease.
Publication TypeJournal Article
Year of Publication2024
AuthorsPulliam L, Sun B, McCafferty E, Soper SA, Witek MA, Hu M, Ford JM, Song S, Kapogiannis D, Glesby MJ, Merenstein D, Tien PC, Freasier H, French A, McKay H, Diaz MM, Ofotokun I, Lake JE, Margolick JB, Kim E-Y, Levine SR, Fischl MA, Li W, Martinson J, Tang N
JournalInt J Mol Sci
Volume25
Issue7
Date Published2024 Mar 29
ISSN1422-0067
KeywordsAlzheimer Disease, COVID-19, Extracellular Vesicles, HIV Infections, Humans, Microfluidics, Pandemics, Post-Acute COVID-19 Syndrome
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.

DOI10.3390/ijms25073830
Alternate JournalInt J Mol Sci
PubMed ID38612641
PubMed Central IDPMC11011771
Grant ListU01 HL146245 / HL / NHLBI NIH HHS / United States
R01 MH121121 / MH / NIMH NIH HHS / United States
U01 HL146208 / HL / NHLBI NIH HHS / United States
UL1 TR001409 / TR / NCATS NIH HHS / United States
KL2 TR001432 / TR / NCATS NIH HHS / United States
U01 HL146192 / HL / NHLBI NIH HHS / United States
U01 HL146242 / HL / NHLBI NIH HHS / United States
TL1 TR001431 / TR / NCATS NIH HHS / United States
I01 CX002322 / CX / CSRD VA / United States
P41 EB020594 / EB / NIBIB NIH HHS / United States
U01 HL146194 / HL / NHLBI NIH HHS / United States
U01 HL146241 / HL / NHLBI NIH HHS / United States
P30 AI027767 / AI / NIAID NIH HHS / United States
P30 AI050409 / AI / NIAID NIH HHS / United States
U01 HL146333 / HL / NHLBI NIH HHS / United States
U01 HL146205 / HL / NHLBI NIH HHS / United States
P30 MH116867 / MH / NIMH NIH HHS / United States
P30 AI073961 / AI / NIAID NIH HHS / United States
U01 HL146201 / HL / NHLBI NIH HHS / United States
P20 GM130423 / GM / NIGMS NIH HHS / United States
IK6 CX002519 / CX / CSRD VA / United States
U01 HL146193 / HL / NHLBI NIH HHS / United States
U01 HL146204 / HL / NHLBI NIH HHS / United States
U01 HL146202 / HL / NHLBI NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States
UL1 TR000004 / TR / NCATS NIH HHS / United States
U01 HL146240 / HL / NHLBI NIH HHS / United States
U01 HL146203 / HL / NHLBI NIH HHS / United States
UL1 TR003098 / TR / NCATS NIH HHS / United States
P30 AI050410 / AI / NIAID NIH HHS / United States