| First Author | Lee J | Year | 2023 |
| Journal | Nat Commun | Volume | 14 |
| Issue | 1 | Pages | 8463 |
| PubMed ID | 38123547 | Mgi Jnum | J:348469 |
| Mgi Id | MGI:7568380 | Doi | 10.1038/s41467-023-44319-3 |
| Citation | Lee J, et al. (2023) ANKS1A regulates LDL receptor-related protein 1 (LRP1)-mediated cerebrovascular clearance in brain endothelial cells. Nat Commun 14(1):8463 |
| abstractText | Brain endothelial LDL receptor-related protein 1 (LRP1) is involved in the clearance of Abeta peptides across the blood-brain barrier (BBB). Here we show that endothelial deficiency of ankyrin repeat and SAM domain containing 1 A (ANKS1A) reduces both the cell surface levels of LRP1 and the Abeta clearance across the BBB. Association of ANKS1A with the NPXY motifs of LRP1 facilitates the transport of LRP1 from the endoplasmic reticulum toward the cell surface. ANKS1A deficiency in an Alzheimer's disease mouse model results in exacerbated Abeta pathology followed by cognitive impairments. These deficits are reversible by gene therapy with brain endothelial-specific ANKS1A. In addition, human induced pluripotent stem cell-derived BBBs (iBBBs) were generated from endothelial cells lacking ANKS1A or carrying the rs6930932 variant. Those iBBBs exhibit both reduced cell surface LRP1 and impaired Abeta clearance. Thus, our findings demonstrate that ANKS1A regulates LRP1-mediated Abeta clearance across the BBB. |
