Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

APOE modulates microglial immunometabolism in response to age, amyloid pathology, and inflammatory challenge

View ORCID ProfileSangderk Lee, View ORCID ProfileNicholas A. Devanney, View ORCID ProfileLesley R. Golden, Cathryn T. Smith, James L. Schwarz, View ORCID ProfileAdeline E. Walsh, Harrison A. Clarke, Danielle S. Goulding, Elizabeth J. Allenger, Gabriella Morillo-Segovia, Cassi M. Friday, Amy A. Gorman, Tara R. Hawkinson, Steven M. MacLean, View ORCID ProfileHolden C. Williams, View ORCID ProfileRamon C. Sun, View ORCID ProfileJosh M. Morganti, View ORCID ProfileLance A. Johnson
doi: https://doi.org/10.1101/2022.05.17.492361
Sangderk Lee
1Department of Physiology, University of Kentucky, Lexington, KY, 40536
2Sanders Brown Center on Aging, University of Kentucky, Lexington, KY, 40536
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Sangderk Lee
Nicholas A. Devanney
1Department of Physiology, University of Kentucky, Lexington, KY, 40536
2Sanders Brown Center on Aging, University of Kentucky, Lexington, KY, 40536
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Nicholas A. Devanney
Lesley R. Golden
1Department of Physiology, University of Kentucky, Lexington, KY, 40536
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Lesley R. Golden
Cathryn T. Smith
1Department of Physiology, University of Kentucky, Lexington, KY, 40536
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
James L. Schwarz
2Sanders Brown Center on Aging, University of Kentucky, Lexington, KY, 40536
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Adeline E. Walsh
1Department of Physiology, University of Kentucky, Lexington, KY, 40536
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Adeline E. Walsh
Harrison A. Clarke
3Department of Neuroscience, University of Kentucky, Lexington, KY, 40536
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Danielle S. Goulding
2Sanders Brown Center on Aging, University of Kentucky, Lexington, KY, 40536
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Elizabeth J. Allenger
1Department of Physiology, University of Kentucky, Lexington, KY, 40536
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gabriella Morillo-Segovia
1Department of Physiology, University of Kentucky, Lexington, KY, 40536
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Cassi M. Friday
1Department of Physiology, University of Kentucky, Lexington, KY, 40536
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Amy A. Gorman
2Sanders Brown Center on Aging, University of Kentucky, Lexington, KY, 40536
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tara R. Hawkinson
3Department of Neuroscience, University of Kentucky, Lexington, KY, 40536
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Steven M. MacLean
1Department of Physiology, University of Kentucky, Lexington, KY, 40536
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Holden C. Williams
1Department of Physiology, University of Kentucky, Lexington, KY, 40536
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Holden C. Williams
Ramon C. Sun
2Sanders Brown Center on Aging, University of Kentucky, Lexington, KY, 40536
3Department of Neuroscience, University of Kentucky, Lexington, KY, 40536
4Markey Cancer Center, University of Kentucky, Lexington, KY, 40536
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ramon C. Sun
Josh M. Morganti
2Sanders Brown Center on Aging, University of Kentucky, Lexington, KY, 40536
3Department of Neuroscience, University of Kentucky, Lexington, KY, 40536
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Josh M. Morganti
  • For correspondence: Johnson.Lance@uky.edu Josh.Morganti@uky.edu
Lance A. Johnson
1Department of Physiology, University of Kentucky, Lexington, KY, 40536
2Sanders Brown Center on Aging, University of Kentucky, Lexington, KY, 40536
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Lance A. Johnson
  • For correspondence: Johnson.Lance@uky.edu Josh.Morganti@uky.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Data/Code
  • Preview PDF
Loading

Summary

The E4 allele of Apolipoprotein E (APOE) is associated with both metabolic dysfunction and a heightened pro-inflammatory response – two findings that may be intrinsically linked through the concept of immunometabolism. Here, we combined bulk, single-cell, and spatial transcriptomics with cell-specific and spatially resolved metabolic analyses to systematically address the role of APOE across age, neuroinflammation, and AD pathology. RNAseq highlighted immunometabolic changes across the APOE4 glial transcriptome, specifically in subsets of metabolically distinct microglia enriched in the E4 brain during aging or following an inflammatory challenge. E4 microglia display increased Hif1α expression, a disrupted TCA cycle, and are inherently pro-glycolytic, while spatial transcriptomics and MALDI mass spectrometry imaging highlight an E4-specific response to amyloid that is characterized by widespread alterations in lipid metabolism. Taken together, our findings emphasize a central role for APOE in regulating microglial immunometabolism.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵* co-first author

  • http://www.ljohnsonlab.com/database.html

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted May 20, 2022.
Download PDF
Data/Code
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
APOE modulates microglial immunometabolism in response to age, amyloid pathology, and inflammatory challenge
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
APOE modulates microglial immunometabolism in response to age, amyloid pathology, and inflammatory challenge
Sangderk Lee, Nicholas A. Devanney, Lesley R. Golden, Cathryn T. Smith, James L. Schwarz, Adeline E. Walsh, Harrison A. Clarke, Danielle S. Goulding, Elizabeth J. Allenger, Gabriella Morillo-Segovia, Cassi M. Friday, Amy A. Gorman, Tara R. Hawkinson, Steven M. MacLean, Holden C. Williams, Ramon C. Sun, Josh M. Morganti, Lance A. Johnson
bioRxiv 2022.05.17.492361; doi: https://doi.org/10.1101/2022.05.17.492361
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
APOE modulates microglial immunometabolism in response to age, amyloid pathology, and inflammatory challenge
Sangderk Lee, Nicholas A. Devanney, Lesley R. Golden, Cathryn T. Smith, James L. Schwarz, Adeline E. Walsh, Harrison A. Clarke, Danielle S. Goulding, Elizabeth J. Allenger, Gabriella Morillo-Segovia, Cassi M. Friday, Amy A. Gorman, Tara R. Hawkinson, Steven M. MacLean, Holden C. Williams, Ramon C. Sun, Josh M. Morganti, Lance A. Johnson
bioRxiv 2022.05.17.492361; doi: https://doi.org/10.1101/2022.05.17.492361

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Neuroscience
Subject Areas
All Articles
  • Animal Behavior and Cognition (3602)
  • Biochemistry (7568)
  • Bioengineering (5523)
  • Bioinformatics (20789)
  • Biophysics (10327)
  • Cancer Biology (7980)
  • Cell Biology (11638)
  • Clinical Trials (138)
  • Developmental Biology (6602)
  • Ecology (10202)
  • Epidemiology (2065)
  • Evolutionary Biology (13615)
  • Genetics (9541)
  • Genomics (12846)
  • Immunology (7920)
  • Microbiology (19541)
  • Molecular Biology (7657)
  • Neuroscience (42093)
  • Paleontology (308)
  • Pathology (1258)
  • Pharmacology and Toxicology (2202)
  • Physiology (3267)
  • Plant Biology (7040)
  • Scientific Communication and Education (1294)
  • Synthetic Biology (1951)
  • Systems Biology (5426)
  • Zoology (1117)