| First Author | Overk CR | Year | 2012 |
| Journal | Neurobiol Dis | Volume | 45 |
| Issue | 1 | Pages | 479-87 |
| PubMed ID | 21945538 | Mgi Jnum | J:180010 |
| Mgi Id | MGI:5304988 | Doi | 10.1016/j.nbd.2011.08.035 |
| Citation | Overk CR, et al. (2012) Effects of aromatase inhibition versus gonadectomy on hippocampal complex amyloid pathology in triple transgenic mice. Neurobiol Dis 45(1):479-87 |
| abstractText | Alzheimer's disease (AD) is the most common form of dementia among the elderly with women exhibiting a higher risk than men for the disease. Due to these gender differences, there is great interest in the role that estrogens play in cognitive impairment and the onset of the classic amyloid and tau lesions in AD. Human and rodent studies indicate a strong association between low brain aromatase, sex hormone levels, and beta amyloid deposition. Therefore, the effects of depleting both circulating and brain estrogen levels, through gonadectomy and/or treatment with the aromatase inhibitor, anastrozole, upon hippocampal AD-like pathology in male and female 3xTgAD mice were evaluated. Liquid chromatography-mass spectrometry revealed anastrozole serum levels of 10.19 ng/mL and for the first time brain levels were detected at 4.7 pg/mL. Densitometric analysis of the hippocampus revealed that anastrozole significantly increased Abeta- but not APP/Abeta-immunoreactivity in intact 3xTgAD females compared to controls (p<0.001). Moreover, anastrozole significantly increased the number of Abeta- compared to APP/Abeta-positive hippocampal CA1 neurons in intact and gonadectomized female mice. Concurrently, anastrozole significantly reduced the APP/Abeta plaque load in 9 month old female 3xTgAD mice. These data suggest that anastrozole treatment differentially affects select amyloid species which in turn may play a role in the extraneuronal to intraneuronal deposition of this peptide. |
