Clearance of beta-amyloid is facilitated by apolipoprotein E and circulating high-density lipoproteins in bioengineered human vessels.
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ABSTRACT: Amyloid plaques, consisting of deposited beta-amyloid (A?), are a neuropathological hallmark of Alzheimer's Disease (AD). Cerebral vessels play a major role in AD, as A? 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-dimensioinal model of CAA in bioengineered human vessels. We show that lipoproteins including brain (apoE) and circulating (high-density lipoprotein, HDL) synergize to facilitate A? transport across bioengineered human cerebral vessels. These lipoproteins facilitate A?42 transport more efficiently than A?40, consistent with A?40 being the primary species that accumulates in CAA. Moreover, apoE4 is less effective than apoE2 in promoting A? transport, also consistent with the well-established role of apoE4 in A? deposition in AD.
SUBMITTER: Robert J
PROVIDER: S-EPMC5634784 | biostudies-literature |
REPOSITORIES: biostudies-literature
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