PSEN1 and Alzheimer disease: To understand the mechanisms underlying the loss of brain endothelial integrity in AD, we used APP/PS1 mice that ubiquitously express a chimeric mouse/human amyloid precursor protein with the familial AD (FAD)-linked “Swedish” mutation (Mo/HuAPP695swe) and FAD-linked mutant human presenilin 1 (PS1DE9) leading to age-dependent accumulation of Aβ peptides in amyloid plaques in the hippocampus and neocortex39–41.