Early formation of mature amyloid-β protein deposits in a mutant APP transgenic model depends on levels of Aβ1–42
Article first published online: 2 NOV 2001
Copyright © 2001 Wiley-Liss, Inc.
Journal of Neuroscience Research
Volume 66, Issue 4, pages 573–582, 15 November 2001
How to Cite
Rockenstein, E., Mallory, M., Mante, M., Sisk, A. and Masliaha, E. (2001), Early formation of mature amyloid-β protein deposits in a mutant APP transgenic model depends on levels of Aβ1–42. J. Neurosci. Res., 66: 573–582. doi: 10.1002/jnr.1247
- Issue published online: 2 NOV 2001
- Article first published online: 2 NOV 2001
- Manuscript Accepted: 6 JUN 2001
- Manuscript Revised: 5 JUN 2001
- Manuscript Received: 7 MAY 2001
- NIH. Grant Numbers: AG10869, AG5131
- EBEWE Pharmaceuticals
- Alzheimer disease;
The main objective of the present study was to develop an alternative singly-transgenic (tg) hAPP model where amyloid deposition will occur at an earlier age. For this purpose, we generated lines of tg mice expressing hAPP751 cDNA containing the London (V717I) and Swedish (K670M/N671L) mutations under the regulatory control of the murine (m)Thy-1 gene (mThy1-hAPP751). In the brains of the highest (line 41) and intermediate (lines 16 and 11) expressers, high levels of hAPP expression were found in neurons in layers 4–5 of the neocortex, hippocampal CA1 and olfactory bulb. As early as 3–4 months of age, line 41 mice developed mature plaques in the frontal cortex, whereas at 5–7 months plaque formation extended to the hippocampus, thalamus and olfactory region. Ultrastructural and double-immunolabeling analysis confirmed that most plaques were mature and contained dystrophic neurites immunoreactive with antibodies against APP, synaptophysin, neurofilament and tau. In addition, a decrease in the number of synaptophysin-immunoreactive terminals was most prominent in the frontal cortex of mice from line 41. Mice from line 11 developed diffuse amyloid deposits at 11 months of age, whereas mice from line 16 did not show evidence of amyloid deposition. Analysis of Aβ by ELISA showed that levels of Aβ1–40 were higher in mice that did not show any amyloid deposits (line 16), whereas Aβ1–42 was the predominant species in tg animals from the lines showing plaque formation (lines 41 and 11). Taken together this study indicates that early onset plaque formation depends on levels of Aβ1–42. J. Neurosci. Res. 66:573–582, 2001. © 2001 Wiley-Liss, Inc.