Differential Cytokine Responses of APOE3 and APOE4 Blood–brain Barrier Cell Types to SARS-CoV-2 Spike Proteins

Abstract

SARS-CoV-2 spike proteins have been shown to cross the blood–brain barrier (BBB) in mice and affect the integrity of human BBB cell models. However, the effects of SARS-CoV-2 spike proteins in relation to sporadic, late onset, Alzheimer’s disease (AD) risk have not been extensively investigated. Here we characterized the individual and combined effects of SARS-CoV-2 spike protein subunits S1 RBD, S1 and S2 on BBB cell types (induced brain endothelial-like cells (iBECs) and astrocytes (iAstrocytes)) generated from induced pluripotent stem cells (iPSCs) harboring low (APOE3 carrier) or high (APOE4 carrier) relative Alzheimer’s risk. We found that treatment with spike proteins did not alter iBE..