Alzheimer’s disease PSEN-2 N141I variant alters trafficking of amyloid beta oligomers in iPSC-derived brain endothelial-like cells
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Intracellular trafficking of amyloid beta oligomers (AβO) in a stem cell-derived brain endothelial-like cell (BEC) model of Alzheimer’s disease (AD) was investigated. Healthy control BECs demonstrated co-localization of cytotoxic AβO in lysosomal compartments whereas AβO was sequestered to late endosomes in AD-BECs. Inhibition of lysosomal activity exacerbated toxicity of AβO in control BECs, but not AD-BECs, suggesting perturbations at the endo-lysosomal interface disrupt lysosomal protection against Aβ in AD BECs.
