Alzheimer's disease (AD) is a prevalent form of dementia, primarily affecting those aged 65 and older, known as late-onset or sporadic AD (sAD). It is characterized by the accumulation of βeta-amyloid protein aggregates and tau protein neurofibrillary tangles. Recent research highlights the crucial link between AD and dysfunction in the blood-brain barrier (BBB), primarily composed of brain endothelial cells (BECs), pericytes, and astrocytes, which regulate homeostasis in the brain. Transporter-mediated regulation at the BBB is pivotal, with dysregulation implicated in AD pathology. Non-invasive techniques like focused ultrasound (FUS) mediated BBB opening are being explored as a potential therapeutic avenue to modulate transporter activity and enhance drug delivery.Here, a human-induced pluripotent stem cells (hiPSCs) from high-risk apolipoprotein E (APOE4) and low-risk APOE3 sAD patients were used to derive brain endothelial-like cells (iBECs) and astrocytes (iAstrocytes). To investigate focused on the expression of key BBB transporters and utilized FUS combined with microbubbles (MBs) to modulate BBB transporters. Results showed significant differences in BBB transporter expression/functionality between APOE4 and APOE3 BBB cells, particularly in those involved in amyloid beta clearance. Following FUS+MB treatment, APOE4 iAstrocytes exhibited higher expression levels of BBB transporters compared to APOE3 immediately after treatment. Untreated APOE4 samples initially had lower expression of BBB transporters compared to APOE3, suggesting a potential compensatory increase in transporter levels due to FUS treatment. These findings highlight the potential of using hiPSC-derived BBB cells to elucidate phenotypic disparities in the BBB of sAD patients, offering insights into potential treatments for sAD patients.