Clearance of beta-amyloid is facilitated by apolipoprotein E and circulating high-density lipoproteins in bioengineered human vessels.
https://elifesciences.org/articles/29595
We’ve long speculated that HDL could counteract the abeta clearance issues present in our genotype. This model confirmed that hypothesis.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-dimensioinal 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.
Interestingly, the combination of anteluminal apoE4 and circulating luminal HDL significantly increased both Aβ40 and Aβ42 transport over 4 hr compared to either Aβ alone or Aβ with apoE4 (Figure 5e–f), and concomitantly the level of Aβ42 accumulated in the tissue at 24 hr was significantly lower in the presence of both apoE4 and HDL compared to Aβ42 alone or Aβ42 and apoE4 (Figure 5h). These results strongly support a cooperative role between brain apoE and circulating HDL to preferentially clear Aβ across the vasculature, and suggest that one beneficial role of circulating HDL is to functionally counteract against apoE4 in this Aβ transport assay.
