Effect of Amyloid-β Driven Blood Brain Barrier Breakdown on Hematopoietic Stem Cell Epigenetic Programming in Alzheimer's

Abstract: Alzheimer’s disease (AD) is a neurodegenerative disorder where harmful amyloid-β (Aβ) proteins build up in the brain. This causes the breakdown of the blood-brain barrier (BBB), which allows hematopoietic stem cell (HSCs) derived peripheral immune cells to infiltrate the brain, leading to neuroinflammation and changes in Aβ dynamics. Stress on the BBB caused by Aβ may lead to the sending of signals to the bone marrow via extracellular vesicles (EVs), which in turn cause a reprogramming in the behavior of the HSCs and alter neuroimmune interactions. This protocol aims to investigate whether EVs derived from the BBB mediate long-distance epigenetic programming of HSCs to create a feedback loop regulating neuroimmune homeostasis.