| First Author | Tai LM | Year | 2013 |
| Journal | J Biol Chem | Volume | 288 |
| Issue | 8 | Pages | 5914-26 |
| PubMed ID | 23293020 | Mgi Jnum | J:196003 |
| Mgi Id | MGI:5486393 | Doi | 10.1074/jbc.M112.442103 |
| Citation | Tai LM, et al. (2013) Levels of soluble apolipoprotein E/amyloid-beta (Abeta) complex are reduced and oligomeric Abeta increased with APOE4 and Alzheimer disease in a transgenic mouse model and human samples. J Biol Chem 288(8):5914-26 |
| abstractText | Human apolipoprotein E (apoE) isoforms may differentially modulate amyloid-beta (Abeta) levels. Evidence suggests physical interactions between apoE and Abeta are partially responsible for these functional effects. However, the apoE/Abeta complex is not a single static structure; rather, it is defined by detection methods. Thus, literature results are inconsistent and difficult to interpret. An ELISA was developed to measure soluble apoE/Abeta in a single, quantitative method and was used to address the hypothesis that reduced levels of soluble apoE/Abeta and an increase in soluble Abeta, specifically oligomeric Abeta (oAbeta), are associated with APOE4 and AD. Previously, soluble Abeta42 and oAbeta levels were greater with APOE4 compared with APOE2/APOE3 in hippocampal homogenates from EFAD transgenic mice (expressing five familial AD mutations and human apoE isoforms). In this study, soluble apoE/Abeta levels were lower in E4FAD mice compared with E2FAD and E3FAD mice, thus providing evidence that apoE/Abeta levels isoform-specifically modulate soluble oAbeta clearance. Similar results were observed in soluble preparations of human cortical synaptosomes; apoE/Abeta levels were lower in AD patients compared with controls and lower with APOE4 in the AD cohort. In human CSF, apoE/Abeta levels were also lower in AD patients and with APOE4 in the AD cohort. Importantly, although total Abeta42 levels decreased in AD patients compared with controls, oAbeta levels increased and were greater with APOE4 in the AD cohort. Overall, apoE isoform-specific formation of soluble apoE/Abeta modulates oAbeta levels, suggesting a basis for APOE4-induced AD risk and a mechanistic approach to AD biomarkers. |
