P1‐052: Immunotherapy in a hypercholesterolemic rabbit model of Alzheimer's disease

acid sequence of beta amyloid (Abeta), which is close to identical to the human sequence. Also, rabbits have an extensively characterized profile on a measure of learning and memory, classical eye blink conditioning, that closely parallels human performance and that is impaired in AD. In two separate studies, we examined the effect of various durations of the cholesterol/ trace copper diet on the development of intracellular Abeta, extracellular Abeta plaques, eye blink conditioning, and the integrity of the blood brain barrier (BBB).Methods: For intracellular brain Abeta and Abeta plaque determination, the research design is shown in Table 1. Rabbits received the cholesterol copper diet in periods varying from 2 to 12 weeks. Immunohistochemistry was used to evaluate brain pathology. EBCC was tested. For BBB studies, rabbits were tested 4 or 10 weeks after cholesterol/trace copper diet onset. Changes in BBB permeability were assessed using the fluorescent tracer, sodium-fluorescein. Results: Intracellular brain Abeta increased with disease progression as shown in Figure 1. In spite of the developing neuropathology, EBCC was not different in rabbits exposed longer to the diet. There was a progression of impairment in the BBB over the 10week course of diet administration, with a 1.6 fold increase in permeability at 4 weeks and over a 4-fold increase in permeability at 10 weeks. Conclusions: Brain pathology increases with longer time on the cholesterol/trace copper diet, and the BBB is impaired in AD model rabbits as it is impaired in human AD. Cognitive changes reflecting the increases of Abeta pathology and BBB impairment were not reflected in EBCC performance.