H. Zheng and H. Xu contributed equally to this paper.
Modulation of Aβ peptides by estrogen in mouse models
Article first published online: 28 DEC 2001
Journal of Neurochemistry
Volume 80, Issue 1, pages 191–196, January 2002
How to Cite
Zheng, H., Xu, H., Uljon, S. N., Gross, R., Hardy, K., Gaynor, J., Lafrancois, J., Simpkins, J., Refolo, L. M., Petanceska, S., Wang, R. and Duff, K. (2002), Modulation of Aβ peptides by estrogen in mouse models. Journal of Neurochemistry, 80: 191–196. doi: 10.1046/j.0022-3042.2001.00690.x
- Issue published online: 28 DEC 2001
- Article first published online: 28 DEC 2001
- Received 3 July, 2001; revised manuscript received 16 October, 2001; accepted 17 October, 2001.
- Alzheimer's disease;
- transgenic mouse
Clinical studies have shown that estrogen deprivation through menopause is a risk factor in both the initiation and progression of Alzheimer's disease (AD) and that estrogen replacement therapy may be protective. One of the major pathological features in the human AD brain is the senile plaque, a proteinaceous structure composed mainly of heterogeneous peptides collectively known as A-beta (Aβ). In vitro studies have linked estrogen with Aβ modulation, suggesting that one-way that estrogen depletion at menopause may exacerbate the features of AD is through Aβ accumulation. To test this, two studies were performed on transgenic models of amyloidosis. Firstly, transgenic mice without detectable amyloid aggregates were subjected to ovariectomy and estradiol supplementation, and Aβ levels were assessed. Secondly, the effects of estrogen modulation were assessed in mice at an age when plaques would be forming initially. Overall, Aβ levels were higher in estrogen-deprived mice than intact mice, and this effect could be reversed through the administration of estradiol. These data suggest that, in vivo, estrogen depletion leads to the accumulation of Aβ in the CNS, which can be reversed through replacement of estradiol. These results provide evidence that post-menopausal estrogen depletion may be linked to an increased risk of AD through Aβ modulation.