BACKGROUND: Recently study indicates a potentially important link between cholesterol, Aβ deposit, and clinicopathological manifestation of Alzheimers disease (AD).OBJECTIVE: To study the effect of high cholesterol diet on cognitive function and neuronal loss of hippocampal dentate gyrus in AD model rats.DESIGN, TIME AND SETTING: A randomized controlled animal study, which was performed in the Laboratory of Stem Cells, Department of Pathology, Third Military Medical University of Chinese PLA from February 2006 to March 2007.MATERIALS: Twenty healthy, male, Wistar rats, aged 3-4 months and weighing (300+20)g, were selected for this study. Aβ1-40 was provided by Sigma Company, USA. Standard diet and high cholesterol diet mixed with cholesterol (5%), sodium hypocholic acid (1%), lard (10%), and ordinary rat food (84%) were provided by Experimental Animal Center, Institute of Field Surgery, Daping Hospital, Third Military Medical University of Chinese PLA.METHODS: Rats were fed on high cholesterol diet or standard diet for eight successive weeks. Then, rats were randomly divided into cholesterol diet+Aβ, high cholesterol diet+phosphate buffered saline (PBS), standard diet+Aβ, and standard diet+PBS group, with five rats in each group. AD rat models were established by local injection of Aβ1-40 solution (10μL) into the hippocampal dentate gyrus. Rats in the control group were injected with the same volume of PBS. After injection, rat were fed for two weeksMAIN OUTCOME MEASURES: Neuronal cells in the hippocampal dentate gyrus were detected by Nissl staining; spatial navigation and spatial probe were detected by Morris water maze to reflect learning and memory.RESULTS: Twenty rats were included in the final analysis, without any loss. (1) Neuronal numbers: neuronal loss in the high cholesterol diet+Aβ and standard diet+Aβ groups was significantly higher than in the PBS groups (Phigh cholesterol diet+PBS group>standard diet+PBS group. Moreover, the number of occasions on which the platform was passed-as well as percentage of swimming distance between two quadrants within two minutes-negatively correlated with average escape latency.CONCLUSION: High cholesterol diet may accelerate neuronal loss in the hippocampal dentate gyrus and aggravate cognitive impairment in AD rats.