ABLIM1 supports cerebrovascular endothelial barrier integrity in an IL-1β-treated hCMEC/D3 model

In Alzheimer’s disease (AD), the role of Actin-binding LIM protein 1 (ABLIM1), which is highly enriched in the brain endothelium, in blood-brain barrier (BBB) dysfunction remains unclear. Our integrative multi-omics analysis, integrating single-cell transcriptomics from AD patient cerebrovascular endothelial cells, transcriptomics from animal models, and vascular endothelial proteomics, identified ABLIM1 as the only overlapping gene across three datasets. We used an inflammatory cell model by treating human cerebral microvascular endothelial cells (hCMEC/D3) with interleukin-1β (IL-1β), which significantly decreased transendothelial electrical resistance (TEER) and markedly reduced ABLIM1 mRNA expression. Furthermore, we identified transcript variants 15 and 16 as the predominant ABLIM1 isoforms in hCMEC/D3 cells. These variants share identical coding sequences and encode the same protein. Lentiviral-mediated knockdown of ABLIM1 significantly impaired barrier integrity, as shown by the reduced TEER, while ABLIM1 overexpression effectively attenuated the IL-1β-induced TEER decrease. Collectively, our findings suggest that ABLIM1 supports cerebrovascular endothelial barrier integrity in an IL-1β-induced inflammatory model, highlighting its potential as a candidate for further investigation in BBB modulation.