Evidence map›Paper›PMID 38771543›Full record

ArticleJournal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology2024

Differential Cytokine Responses of APOE3 and APOE4 Blood-brain Barrier Cell Types to SARS-CoV-2 Spike Proteins.

Juliana C S Chaves, Laura A Milton, Romal Stewart, Tarosi Senapati, Laura M Rantanen, Joanna M Wasielewska, Serine Lee, Damián Hernández, Lachlan McInnes, Hazel Quek and 4 more

Abstract read
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In one paragraph

Article in Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Juliana C S ChavesMental Health and Neuroscience Program, QIMR Berghofer Medical Research Institute, Brisbane (QLD), Australia.
Laura A MiltonMental Health and Neuroscience Program, QIMR Berghofer Medical Research Institute, Brisbane (QLD), Australia.
Romal StewartMental Health and Neuroscience Program, QIMR Berghofer Medical Research Institute, Brisbane (QLD), Australia.
Tarosi SenapatiThe University of Queensland, Brisbane (QLD), Australia.
Laura M RantanenMental Health and Neuroscience Program, QIMR Berghofer Medical Research Institute, Brisbane (QLD), Australia.
Joanna M WasielewskaMental Health and Neuroscience Program, QIMR Berghofer Medical Research Institute, Brisbane (QLD), Australia.
Serine LeeMental Health and Neuroscience Program, QIMR Berghofer Medical Research Institute, Brisbane (QLD), Australia.
Damián HernándezDepartment of Anatomy and Physiology, The University of Melbourne, Parkville (VIC), Australia.
Lachlan McInnesSchool of Chemistry, Bio21 Institute for Molecular Science and Biotechnology, The University of Melbourne, Parkville (VIC), Australia.
Hazel QuekMental Health and Neuroscience Program, QIMR Berghofer Medical Research Institute, Brisbane (QLD), Australia.
Alice PébayDepartment of Anatomy and Physiology, The University of Melbourne, Parkville (VIC), Australia.
Paul S DonnellySchool of Chemistry, Bio21 Institute for Molecular Science and Biotechnology, The University of Melbourne, Parkville (VIC), Australia.
Anthony R WhiteMental Health and Neuroscience Program, QIMR Berghofer Medical Research Institute, Brisbane (QLD), Australia.
Lotta E OikariMental Health and Neuroscience Program, QIMR Berghofer Medical Research Institute, Brisbane (QLD), Australia. Lotta.Oikari@qimrberghofer.edu.au.

Funding

National Health and Medical Research Council 1154389National Health and Medical Research Council APP1118452
6 · The paper itself

Abstract

SARS-CoV-2 spike proteins have been shown to cross the blood-brain barrier (BBB) in mice and affect the integrity of human BBB cell models. However, the effects of SARS-CoV-2 spike proteins in relation to sporadic, late onset, Alzheimer's disease (AD) risk have not been extensively investigated. Here we characterized the individual and combined effects of SARS-CoV-2 spike protein subunits S1 RBD, S1 and S2 on BBB cell types (induced brain endothelial-like cells (iBECs) and astrocytes (iAstrocytes)) generated from induced pluripotent stem cells (iPSCs) harboring low (APOE3 carrier) or high (APOE4 carrier) relative Alzheimer's risk. We found that treatment with spike proteins did not alter iBEC integrity, although they induced the expression of several inflammatory cytokines. iAstrocytes exhibited a robust inflammatory response to SARS-CoV-2 spike protein treatment, with differences found in the levels of cytokine secretion between spike protein-treated APOE3 and APOE4 iAstrocytes. Finally, we tested the effects of potentially anti-inflammatory drugs during SARS-CoV-2 spike protein exposure in iAstrocytes, and discovered different responses between spike protein treated APOE4 iAstrocytes and APOE3 iAstrocytes, specifically in relation to IL-6, IL-8 and CCL2 secretion. Overall, our results indicate that APOE3 and APOE4 iAstrocytes respond differently to anti-inflammatory drug treatment during SARS-CoV-2 spike protein exposure with potential implications to therapeutic responses.

Indexed as

Apolipoprotein E3Apolipoprotein E4AstrocytesBlood-Brain BarrierCytokinesSpike Glycoprotein, CoronavirusCells, CulturedCOVID-19Endothelial CellsHumansInduced Pluripotent Stem CellsSARS-CoV-2Apolipoprotein E3Apolipoprotein E4CytokinesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2Alzheimer’s diseaseApolipoprotein EAstrocyteBlood–brain barrierBrain endothelial cellSARS-CoV-2

Identifiers

PMID38771543

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.