| First Author | Zou K | Year | 2013 |
| Journal | Am J Pathol | Volume | 182 |
| Issue | 6 | Pages | 2322-31 |
| PubMed ID | 23562443 | Mgi Jnum | J:198537 |
| Mgi Id | MGI:5496982 | Doi | 10.1016/j.ajpath.2013.01.053 |
| Citation | Zou K, et al. (2013) Abeta43 is the earliest-depositing Abeta species in APP transgenic mouse brain and is converted to Abeta41 by two active domains of ACE. Am J Pathol 182(6):2322-31 |
| abstractText | Amyloid-beta protein (Abeta) varies in length at its carboxyl terminus. The longer Abeta species, Abeta43 and Abeta42, are highly amyloidogenic and deposit more frequently than Abeta40 in the brain of Alzheimer disease (AD) patients. However, the characterization of Abeta43 deposition in the brain and the relationship between Abeta43 and Abeta42 or Abeta40 remain unclear. We provide evidence that Abeta43 deposition appears earlier than Abeta42 and Abeta40 deposition in the brain of mutant amyloid precursor protein transgenic (APPtg) mice, suggesting that Abeta43 is the earliest-depositing species. In addition, we found increased Abeta43 levels and Abeta43/Abeta42 ratios in the serum of AD patients, suggesting their use as diagnostic blood biomarkers for AD. We further show that angiotensin-converting enzyme (ACE) converts Abeta43 to Abeta41. Notably, this Abeta43-to-Abeta41 converting activity requires two active domains of ACE. Inhibition of ACE activity significantly enhanced Abeta43 deposition in APPtg mouse brain. Our results suggest that Abeta43 is the earliest-depositing species in brain parenchyma and that Abeta43 may trigger later Abeta42 and Abeta40 deposition or may be converted to Abeta42 and Abeta40 plaques. Activities of both ACE domains may be important for reducing Abeta43 levels in serum and reducing brain Abeta43 deposition. |
