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KMID : 0606920070150010034
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Biomolecules & Therapeutics
2007 Volume.15 No. 1 p.34 ~ p.39
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Increase of Amyloid-Beta Peptide Generation in High Cholesterol Diet Rabbit Brain
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Lee Yong-Kyoung
Son Dong-Ju
Lee Jae-Woong
Lee Hyung-Woo
Yun Young-Won
Oh Ki-Wan
Hong Jin-Tae
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Abstract
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Alzheimer’s disease (AD) is an abnormal accumulation of the ${\beta}$-amyloid protein $(A{\beta})$ in specific brain region. It has been speculated that disturbance in cholesterol homeostasis may contribute to the etiology of AD by increasing $A{\beta}$ generation. However, conclusive evidence and possible mechanism has not been reported. In the present study, we demonstrated that rabbits treated with 0.5% cholesterol for 16 weeks increased serum total cholesterol, triacylglycerol, and low-density lipoprotein levels. $A{\beta}$ levels is higher in the hippocampus of brain in cholesterol dieted rabbits than that of normal diet rabbis. Expression and activities of ${\beta}-$ and ${\gamma}-$ secretases, the enzymes that cleave ${\beta}$-amyloid precursor protein to generate $A{\beta}$, were also increased in hippocampus of high cholesterol dieted rabbit than those of normal dieted rabbits. Our results suggest that high cholesterol diet may be associated with increased $A{\beta}$ accumulation in the brain of rabbits, and suggest that high cholesterol diet may be causal factor in the development or progression of AD.
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KEYWORD
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Alzheimer’s disease, high cholesterol diet, beta-amyloid, ${\beta}-$ and ${\gamma}-$ secretase, rabbit
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