A HUMAN APOE MOUSE MODEL OF ALZHEIMER?S DISEASE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The mice involved in this project are 21-23 month old human apoE3 and E4 targeted replacement mice on a C57Bl6 background. We have observed enlarged lateral ventricles in the brains of 18 mo. old human apoE4 mice (compared to apoE3 mice) based on histological sections and would like to confirm using brain imaging on live animals. We have several other indicators of Alzheimer's-like dementia in the aged apoE4 mice such as behavioral and electrophysiological deficits. Furthermore, the apoE4 mice have significantly higher number of intracerebral hemorrhages, gliosis and immunocytochemical markers of synaptic dysfunction. If we are able to demonstrate significant enlargement of the lateral (or other) ventricles in these mice vs controls, it would be a very important discovery, strengthening the evidence for these mice to be used as models of AD.