| First Author | Ringland C | Year | 2020 |
| Journal | Neurobiol Aging | Volume | 95 |
| Pages | 56-68 | PubMed ID | 32758917 |
| Mgi Jnum | J:299539 | Mgi Id | MGI:6501318 |
| Doi | 10.1016/j.neurobiolaging.2020.06.018 | Citation | Ringland C, et al. (2020) Apolipoprotein E isoforms differentially regulate matrix metallopeptidase 9 function in Alzheimer's disease. Neurobiol Aging 95:56-68 |
| abstractText | Apolipoprotein E (APOE) has been shown to influence amyloid-beta (Abeta) clearance from the brain in an isoform-specific manner. Our prior work showed that Abeta transit across the blood-brain-barrier was reduced by apoE4, compared to other apoE isoforms, due to elevated lipoprotein receptor shedding in brain endothelia. Recently, we demonstrated that matrix metallopeptidase 9 (MMP-9) induces lipoprotein receptor proteolysis in an apoE isoform-dependent manner, which impacts Abeta elimination from the brain. The current studies interrogated the relationship between apoE and MMP-9 and found that apoE impacted proMMP-9 cellular secretion from brain endothelia (apoE2 < apoE3 = apoE4). In a cell-free assay, apoE dose-dependently reduced MMP-9 activity, with apoE4 showing a significantly weaker ability to inhibit MMP-9 function than apoE2 or apoE3. Finally, we observed elevated MMP-9 expression and activity in the cerebrovasculature of both human and animal AD brain specimens with an APOE4 genotype. Collectively, these findings suggest a role for apoE in regulating MMP-9 disposition and may describe the effect of apoE4 on Abeta pathology in the AD brain. |
