This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The A protein is an important factor in the early development of Alzheimer's disease, a dementing disorder of old age that tends to affect women more than men. In Alzheimer's disease, A aggregates into abnormal structures called senile plaques, as well as smaller, toxic assemblies called oligomers. We hypothesize that the amount of A in the brain may be increased by the hormonal changes that accompany menopause. In this study, we are studying a mouse model that has been genetically engineered to produce human A . We have used a chemical called VCD, which selectively depletes certain cells in the ovary, to create a hormonal state that resembles menopause. We recently completed the first in vivo phase of our subproject, in which treated mice slowly stopped cycling over a period of several months following VCD administration. Preliminary immunohistochemical analysis of brains from the first group of mice indicate that both experimental and control mice have senile plaques in the brain, and that the number of senile plaques is similar in menopausal and normal mice. A second phase of the study is ongoing, in which we are studying mice that have had their ovaries removed. When the second phase is completed, we will analyze all brains for A using MALDI-TOF. Meanwhile, we are working on a protocol for analyzing synthetic A by MALDI-TOF. We expect that in-depth analysis of A by MALDI-TOF will demonstrate differences in subtypes of the A protein.
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