[Abstract Title]. - Society for Neuroscience

Authors: *R. LI, C. MCALLISTER, J. DOLE, J. LONG;
LJ Roberts Ctr. Alzheimers, Sun Hlth. Res. Inst., Sun City, AZ
Abstract: While both menopause and andropause refer to the decrease in sex steroids upon
reproductive senescence in women and men, respectively, the rate at which these changes take
place are drastically different, with menopause occurring very abruptly while the process of
andropause is a gradual phenomenon. In fact, this gender-based difference in the rate and
intensity of hormonal changes due to reproductive aging serves as the basis for hypotheses
regarding the role of sex steroids in Alzheimer‟s disease (AD). Several recent studies have
reported that low bioavailable testosterone is associated with AD in aged men. Testosterone
administration in elderly men might help to improve their cognitive function. Because
testosterone in the brain is converted into estradiol by a single enzyme, aromatase, to further
identify and understand the underlying mechanism of testosterone in AD, we generated a new
animal model using a gene-based approach, by crossing aromatase gene knockout mice with
APP23 transgenic mice to produce sex hormone disrupted APP23 mice (APP/Ar+/-). Compared
to APP23 transgenic control mice, the male APP23/Ar+/- mice exhibited a large increase in brain
testosterone and a significant reduction in estrogen. Instead of an early-onset and increased Aβ
deposition as is found in female APP23/Ar+/- mice, we found a significant delay in brain plaque
formation in the male APP23/Ar+/- mice. These male mice also exhibited increased Aβ
clearance/degradation and changes in Aβ metabolism compared to APP23 control mice. We
examined cognitive behavior and our data suggest that increasing endogenous testosterone level
not only prevents cognitive deficits in AD model mice, but also improves cognitive function
compared to wildtype. Our results indicate that endogenous testosterone in the male brain may
play a significant neuroprotective role in AD neuropathology.
Disclosures: R. Li, None; C. McAllister, None; J. Long, None; J. Dole, None.
Poster
243. Abeta Assembly and Deposition
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 243.10/K4
Topic: C.01.b. Abeta assembly and deposition
Support: NIH Grant AG25323
NIH Grant MH59786
Title: Elucidating the roles of small molecules in modulating the dynamic assembly of Aß in
solution by electrospray ionization high resolution mass spectrometry