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Cited by 45Alzheimer's disease research and treatmentsBarrier Structure and Function StudiesNeuroinflammation and Neurodegeneration Mechanisms

Monomeric C‐reactive protein via endothelial CD31 for neurovascular inflammation in an ApoE genotype‐dependent pattern: A risk factor for Alzheimer’s disease?

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Zhang, Zhengrong, Na, Hana, Gan, Qini, Tao, Qiushan, Alekseyev, Yuriy, Hu, Junming, Yan, Zili, Yang, Jack B. +11 more·2021·Aging Cell
DOI 10.1111/acel.13501PMC PMC8590103
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Abstract

In chronic peripheral inflammation, endothelia in brain capillary beds could play a role for the apolipoprotein E4 (ApoE4)‐mediated risk for Alzheimer's disease (AD) risk. Using human brain tissues, here we demonstrate that the interactions of endothelial CD31 with monomeric C‐reactive protein (mCRP) versus ApoE were linked with shortened neurovasculature for AD pathology and cognition. Using ApoE knock‐in mice, we discovered that intraperitoneal injection of mCRP, via binding to CD31 on endothelial surface and increased CD31 phosphorylation (pCD31), leading to cerebrovascular damage and the extravasation of T lymphocytes into the ApoE4 brain. While mCRP was bound to endothelial CD31 in a dose‐ and time‐dependent manner, knockdown of CD31 significantly decreased mCRP binding and altered the expressions of vascular‐inflammatory factors including vWF, NF‐κB and p‐eNOS. RNAseq revealed endothelial pathways related to oxidative phosphorylation and AD pathogenesis were enhanced, but endothelial pathways involving in epigenetics and vasculogenesis were inhibited in ApoE4. This is the first report providing some evidence on the ApoE4‐mCRP‐CD31 pathway for the cross talk between peripheral inflammation and cerebrovasculature leading to AD risk.

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Cited by

Sorted by citations

Authors
Zhang, Z., Na, H., Gan, Q., Tao, Q., Alekseyev, Y., Hu, J., Yan, Z., Yang, J. B., Tian, H., Zhu, S., Li, Q., Rajab, I. M., Blusztajn, J. K., Wolozin, B., Emili, A., Zhang, X., Stein, T., Potempa, L. A., & Qiu, W. Q.
Affiliations
  • Boston University (US)
  • Roosevelt University (US)
  • Department of Pathology and Laboratory Medicine Boston University School of Medicine Boston Massachusetts USA
Corresponding author
Qiu, Wei Qiao
ORCID
Venue
Aging Cell
Publisher
Wiley
Published
2021-10-23
Volume
20
Issue
11
Pages
e13501-e13501
ISSN
  • 1474-9718 (ISSN-L)
  • 1474-9726
DOI
10.1111/acel.13501
PMC
PMC8590103
OpenAlex
W3207019565
Cited by
45
References
6
Citations by year
2026: 6 · 2025: 7 · 2024: 10 · 2023: 14 · 2022: 7 · 2021: 1
FWCI
5.03
Type
journal article
Language
en
Open access
Licence
Locations
  • Aging Cell (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Institute of Neurological Disorders and Stroke (N01‐HC‐25195, NS‐17950)
  • National Heart, Lung, and Blood Institute (N01‐HC‐25195)
  • National Institute on Aging (AG‐008122, AG‐022476, AG‐16495, P30 AG13864, R01 AG054546, R21AG045757, R56AG059805, RO1AG‐022476)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
monomeric C-reactive protein, CD31, APOE ε4, Alzheimer's disease risk, neurovascular inflammation, endothelial dysfunction, cerebrovascular injury, peripheral inflammation, oxidative phosphorylation, NF-κB, endothelial nitric oxide synthase, von Willebrand factor, vasculogenesis, epigenetics
MeSH terms
Mice, Knockout, ApoE, Adult, Aged, Aged, 80 and over, Alzheimer Disease, Animals, Apolipoproteins E, Brain, C-Reactive Protein, Cells, Cultured, Female, Genotype, Humans, Inflammation, Male, Mice, Inbred C57BL, Middle Aged, Oxidative Phosphorylation, Risk Factors, Signal Transduction, Case-Control Studies, Platelet Endothelial Cell Adhesion Molecule-1, Endothelial Cells, Mice, Apolipoprotein E4, Gene Knockdown Techniques, Gene Knock-In Techniques

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