First functional 3-dimensional CAA-model in bioengineered human vessels
Can artificial blood vessels grown from human cells shed light on amyloid buildup in the Alzheimer’s brain? Yes, they can, according to researchers led by Cheryl Wellington at the University of British Columbia, Vancouver, Canada. They seeded a tube-shaped scaffold with human endothelial cells, smooth muscle cells, and astrocytes to create artificial arteries through which they pumped media. To model cerebral amyloid angiopathy, an accumulation of Aβ in brain blood vessel walls, they added Aβ40 and Aβ42. Both peptides accumulated in the vessel tissue, eventually forming fibrils. But the cells also transported some of the Aβ into the vessel lumen, with ApoE and high-density lipoprotein preferentially facilitating transport of Aβ42 over Aβ40.
Aβ transport across bioengineered human cerebral vessels
Cerebral vessels play a major role in Alzheimer’s disease, as Aβ is cleared from the brain by pathways involving the cerebrovasculature, most AD patients have cerebrovascular amyloid (cerebral amyloid angiopathy (CAA), and cardiovascular risk factors increase dementia risk. The researchers present a notable advance in vascular tissue engineering by generating the first functional 3-dimensioinal model of CAA in bioengineered human vessels. They show that lipoproteins including brain (apoE) and circulating (high-density lipoprotein, HDL) synergize to facilitate Aβ transport across bioengineered human cerebral vessels. These lipoproteins facilitate Aβ42 transport more efficiently than Aβ40, consistent with Aβ40 being the primary species that accumulates in CAA. Moreover, apoE4 is less effective than apoE2 in promoting Aβ transport, also consistent with the well-established role of apoE4 in Aβ deposition in AD.
Source: Alzforum | 10 October 2017