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P2‐482: Effects of ZC plus hormone treatment on a transgenic mouse model of Alzheimer's disease
Author(s) -
Mendoza Kriscelle,
Schultz James,
O'Barr Stephen
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.05.1353
Subject(s) - genetically modified mouse , hormone , transgene , biomarker , medicine , endocrinology , morris water navigation task , dementia , water maze , amyloid beta , disease , hippocampus , psychology , chemistry , biochemistry , gene
Background: Alzheimer’s Disease (AD) is the sixth leading cause of death in the United States and comprises about 70% of all dementia cases. Although there is no known cause for AD, memory loss has been linked to amyloid beta (Aß) deposition in the AD brain. AD mouse models have been generated to express this Aß pathology, and are used to study changes in cognitive behavior. In the present study, our group has treated an AD mouse model (R1.40) with a novel drug, zinc plus cyclo(his-pro) (ZC) in conjunction with hormone treatment to test their effects on biomarker levels and cognitive behavior.Methods:Nine to twelve month old huAPP-YAC transgenic mice (R1.40 strain) were treated for six months with 10 ml/L Zn plus 1.9 mg/L cyclo(his-pro) (ZC) in water ad libitum and/or treated with subcutaneous hormone pellets. Non-treated transgenic animals were sham operated and given access to non-treated water. Mice were then tested on a Barnes Maze and analyzed for learning and working memory over a 6 month period of time. At the end of testing, brains were harvested and analyzed by ELISA and for enzyme activity (IDE). Results: Analyses of experimental groups show that the novel formulation ZC and hormone treatment alters learning behavior and AD specific biomarker expression in the R1.40 transgenic mouse model of AD. The animals treated with hormone and with ZC found the target hole of the Barnes maze in a shorter amount of time compared to the untreated, transgenic controls. Hormone and ZC treated animals also had significantly higher IDE enzyme activity compared to the non-treated transgenic controls, suggesting a potential to reduce AD specific pathology.Conclusions:This study shows that the novel drug, ZC in conjunction with hormone treatment, may be beneficial to patients who are in the earlier stages of Alzheimer’s disease.