Differential endothelial cell remodeling in Down syndrome and APP duplication drives distinct blood brain barrier dysfunction

Down syndrome and APP duplication both increase Aβ40/Aβ42 secretion in human iPSC-derived endothelial cells, but DS preserves junctional integrity while APPdup shows higher permeability.

• Why it matters: Extra APP dosage is linked to Alzheimer disease and cerebral amyloid angiopathy, yet how endothelial remodeling differs between DS and APPdup—and shapes blood brain barrier dysfunction—remains unclear.
• What they did: The study compared DS and APPdup iECs to matched isogenic controls, measuring morphology, junctional proteins, Aβ peptide secretion, barrier permeability, and transcriptomic pathway enrichment.
• The result: DS iECs had increased junctional protein expression and reduced permeability with extensive transcriptomic dysregulation, while APPdup iECs showed milder changes and increased permeability, implying distinct BBB resilience during ageing.

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