Dataset Information

The Influences of ApoE Isoforms on Endothelial Adherens Junctions and Actin Cytoskeleton Responding to mCRP

ABSTRACT: Monomeric C-reactive protein (mCRP) plays a role in cerebrovascular damage mediated by apolipoprotein E4 (ApoE4) in Alzheimer's disease (AD) pathogenesis. Using proteomic profilings, we found altered cytoskeleton proteins in the microvasculature of AD brains, including increased levels of hyperphosphorylated tau (pTau) and the actin-related protein, LIMA1. To address the hypothesis that cytoskeletal changes serve as early pathological signatures in brain endothelia for AD, ApoE4 knock-in mice intraperitoneal injected with mCRP revealed that mCRP bound to CD31 to increase LIMA1 expression and facilitate the binding of phosphorylated CD31 (pCD31) to LIMA1. mCRP combined with APOE4 protein altered the expression of various actin cytoskeleton proteins along with decreased interaction of CD31 and VE-Cadherin, causing microvasculature damage. Notably, the APOE2 protein attenuated these changes. Overall, the ApoE4-mCRP-CD31 pathway acts via pCD31-LIMA1 interaction to disrupt the adherens junctions and the actin cytoskeleton, leading to endothelial barrier dysfunction in the brain and increased AD risk.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

TISSUE(S): Brain, Epithelial Cell

DISEASE(S): Alzheimer's Disease

SUBMITTER: WEIWEI LIN

LAB HEAD: Weiwei Lin

PROVIDER: PXD051529 | Pride | 2025-05-06

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20210314_WL_Wendy_HMves_1D_TMT_phos.raw	Raw
	20210314_WL_Wendy_MBves_1D_TMT_prot.raw.raw	Raw
	Human_Phosphoproteome_searchingFiles.zip	Other
	Mouse_Proteome_searchingFiles.zip	Other

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Publications

The influences of ApoE isoforms on endothelial adherens junctions and actin cytoskeleton responding to mCRP.

Zhang Zhengrong Z Lin Weiwei W Gan Qini Q Lei Maohua M Gong Bin B Zhang Chao C Henrique Jessica Salles JS Han Jingyan J Tian Hua H Tao Qiushan Q Potempa Lawrence A LA Stein Thor D TD Emili Andrew A Qiu Wei Qiao WQ

Angiogenesis 20240914 4

Apolipoprotein E4 (ApoE4) plays an important role responding to monomeric C-reactive protein (mCRP) via binding to CD31 leading to cerebrovascular damage and Alzheimer's disease (AD). Using phosphor-proteomic profiling, we found altered cytoskeleton proteins in the microvasculature of AD brains, including increased levels of hyperphosphorylated tau (pTau) and the actin-related protein, LIMA1. To address the hypothesis that cytoskeletal changes serve as early pathological signatures linked with C ...[more]

PMID: 39276310

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