Presentation description

Inhibiting the function of the molecular target Arf6 has been shown to improve Multiple Sclerosis (MS) symptoms, stabilize the blood-brain barrier (BBB), attenuate inflammation, and preserve immune function in a mouse model of the disease. However, the role of Arf6 in other neuroinflammatory diseases, such as Alzheimer's disease, remains unclear. Alzheimer's disease is the leading cause of dementia and is characterized by a buildup of amyloid beta plaques and neurofibrillary tangles in the brain. Amyloid-beta efflux transporters, such as LRP1 and P-glycoprotein, are critical in clearing waste across the BBB and preventing amyloid-beta buildup. In Alzheimer's disease, inflammatory conditions drive a process called EndoMT, where endothelial cells adopt mesenchymal characteristics in a process that can contribute to BBB breakdown. Using cell culture techniques, we modeled the cerebrovascular environment of the BBB in Alzheimer's disease by exposing human brain microvascular endothelial cells to inflammatory conditions to induce EndoMT. We transfected the cells with adenoviruses to modulate Arf6 function, and subsequently observed the expression of amyloid-beta efflux transporters using Western Blot. Our hypothesis is that cells undergoing EndoMT exhibit downregulated expression of these critical transporters. We further hypothesize that inhibiting Arf6 function may help stabilize the BBB and possibly preserve amyloid-beta efflux transporter expression. Our results will reveal any links between EndoMT, BBB breakdown, and amyloid-beta accumulation. They will also illuminate the role of Arf6 in this process to ultimately improve our mechanistic understanding of Alzheimer's disease.