Cholesterol increases ventricular volume in a rabbit model of Alzheimer's disease.

One of the hallmarks of Alzheimer's disease is a significant increase in ventricular volume. To date we and others have shown that a cholesterol-fed rabbit model of Alzheimer's disease displays as many as fourteen different pathological markers of Alzheimer's disease including amyloid-β accumulation, thioflavin-S staining, blood brain barrier breach, microglia activation, cerebrovasculature changes, and alterations in learning and memory. Using structural magnetic resonance imaging at 3T, we now report that cholesterol-fed rabbits also show a significant increase in ventricular volume following 10 weeks on a diet of 2% cholesterol. The increase in volume is attributable in large part to increases in the size of the third ventricle. These changes are accompanied by significant increases in the number of amyloid-β immuno-positive cells in the cortex and hippocampus. Increases in the number of amyloid-β neurons in the cortex also occurred with the addition of 0.24 ppm copper to the drinking water. Together with a list of other pathological markers, the current results add further validity to the value of the cholesterol-fed rabbit as a non-transgenic animal model of Alzheimer's disease.