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

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 th

SUBMITTER: Zhang Z 

PROVIDER: S-EPMC8590103 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature