Amyloid-β1-42 oligomers compromise oligodendrocyte precursor cells and disrupt blood–brain barrier integrity in vitro

Amyloid-β (Aβ), particularly the aggregation-prone Aβ1-42, plays a central role in Alzheimer’s disease (AD). While its neuronal toxicity is well known, effects on glial and vascular cells remain unclear. To investigate how Aβ1-42 oligomers affect oligodendrocyte precursor cells (OPCs), pericytes (PCs), and endothelial cells (ECs), and how these effects contribute to blood–brain barrier (BBB) dysfunction. In vitro assays were used to assess cell viability and BBB integrity following Aβ exposure. Transcriptomic profiling was performed on Aβ1-42-treated OPCs. Transendothelial electrical resistance (TEER) was used to measure barrier function. Aβ1-42, but not Aβ1-40, induced cytotoxicity in OPCs and PCs. ECs showed impaired barrier function without cell death. Aβ1-42-treated OPCs upregulated pro-inflammatory genes ( Mmp9 , Il1b ) and downregulated genes related to cell cycle and growth signaling. Conditioned media from Aβ-exposed OPCs and PCs reduced TEER in ECs, indicating paracrine-mediated BBB disruption. These findings demonstrate that Aβ1-42 oligomers impair BBB integrity under in vitro conditions through both direct and non-cell autonomous mechanisms. Further in vivo studies are warranted to validate the relevance of these mechanisms in AD pathogenesis.