Alzheimer's On a Chip: Engineering Brain Vessels to Unravel Dementia's Bleeding Mysteries

Abstract

Alzheimer's disease (AD) is a growing public health concern, projected to affect over 15 million Americans within the next decade. A critical hallmark of AD is the accumulation of amyloid-beta (Aβ) plaques, which disrupt neural cells and contribute to vascular abnormalities and brain bleeds. This study aims to develop an in vitro model focusing on vascular smooth muscle cells (VSMCs) to understand how cerebral blood vessels are impacted in AD. Using Organ-on-a-Chip technology, the μSiM platform was employed to investigate Aβ's effects on VSMCs. Results indicated that prolonged Aβ exposure deteriorates VSMCs, weakening brain blood vessels and creating conditions conducive to brain bleeds. The μSiM platform demonstrated its potential as a viable tool for modeling AD and vascular dementia, with future work set to incorporate co-culturing with other brain cells to enhance model accuracy. These findings contribute to understanding the vascular aspects of AD and lay the groundwork for developing drug-testing platforms targeting this mechanism.