Differentiation of disease-specific induced pluripotent stem cells into a blood-brain barrier system analyzing the role of APOE4 in Alzheimer's disease

The risk for Alzheimer's disease (AD), the most common type of dementia, increases with age resulting in a major challenge for the ageing society. Dysfunction of the blood-brain barrier (BBB) contributes to AD progression and the characteristic accumulation of amyloid-β (Aβ) peptides. Recently, genome-wide association studies (GWAS) with participation of our research team revealed a significant association between the ATP-binding cassette transporter A7 (ABCA7) and the late-onset form of AD (LOAD). It was shown that ABCA7 is involved in Aβ homeostasis, lipid metabolism, and phagocytosis, but the detailed role in LOAD still remains unclear. The generation of patient-derived, disease-specific induced pluripotent stem (iPS) cells followed by the differentiation into cells of the BBB is a valuable approach to study disease mechanisms related to ABCA7 during the pathogenesis of AD.