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- Title
Clearance of beta-amyloid is facilitated by apolipoprotein E and circulating high-density lipoproteins in bioengineered human vessels.
- Authors
Robert, Jerome; Button, Emily B.; Yuen, Brian; Gilmour, Megan; Kang, Kevin; Bahrabadi, Arvin; Stukas, Sophie; Wenchen Zhao; Kulic, Iva; Wellington, Cheryl L.
- Abstract
Amyloid plaques, consisting of deposited beta-amyloid (Aβ), are a neuropathological hallmark of Alzheimer's Disease (AD). Cerebral vessels play a major role in AD, 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. Here we present a notable advance in vascular tissue engineering by generating the first functional 3-dimensional model of CAA in bioengineered human vessels. We 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.
- Subjects
AMYLOID beta-protein; ALZHEIMER'S disease; AMYLOID plaque; CEREBRAL amyloid angiopathy; HIGH density lipoproteins; TISSUE engineering
- Publication
eLife, 2017, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.29595