Use of copper and insulin-resistance to accelerate cognitive deficits and synaptic protein loss in a rat Abeta-infusion Alzheimer's disease model (original) (raw)

2008

Abstract

The rat amyloid-beta (Abeta) intracerebroventricular infusion can model aspects of Alzheimer's disease (AD) and has predicted efficacy of therapies such as ibuprofen and curcumin in transgenic mouse models. High density lipoprotein (HDL), a normal plasma carrier of Abeta, is used to attenuate Abeta aggregation within the pump, causing Abeta-dependent toxicity and cognitive deficits within 3 months. Our goal was to identify factors that might accelerate onset of Abeta-dependent deficits to improve efficiency and cost-effectiveness of model. We focused on: 1) optimizing HDL-Abeta preparation for maximal toxicity; 2) evaluating the role of copper, a factor typically in water that can impact oligomer stability; and 3) determining impact of insulin resistance (type II diabetes), a risk factor for AD. In vitro studies were performed to determine doses of copper and methods of Abeta-HDL preparation that maximized toxicity. These preparations when infused resulted in earlier onset of co...

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