Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Increase of Amyloid-Beta Peptide Generation in High Cholesterol Diet Rabbit Brain

  • Lee, Yong-Kyoung (College of Pharmacy, Chungbuk National University) ;
  • Son, Dong-Ju (College of Pharmacy, Chungbuk National University) ;
  • Lee, Jae-Woong (College of Pharmacy, Chungbuk National University, CBITRC, Chungbuk National University) ;
  • Lee, Hyung-Woo (College of Pharmacy, Chungbuk National University) ;
  • Yun, Young-Won (College of Veterinary Medicine, Chungbuk National University) ;
  • Oh, Ki-Wan (College of Pharmacy, Chungbuk National University) ;
  • Hong, Jin-Tae (College of Pharmacy, Chungbuk National University, CBITRC, Chungbuk National University)
  • Published : 2007.03.30
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Abstract

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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References

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