Human apoB overexpression and a high-cholesterol diet differently modify the brain APP metabolism in the transgenic mouse model of atherosclerosis.

Abstract

Epidemiological and biochemical data suggest a link between the cholesterol metabolism, the amyloid precursor protein (APP) processing and the increased cerebral beta-amyloid (Abeta) deposition in Alzheimer's disease (AD). The individual and combined effects of a high-cholesterol (HC) diet and the overexpression of the human apoB-100 gene were therefore examined on the cerebral expression and processing of APP in homozygous apoB-100 transgenic mice [Tg (apoB(+/+))], a validated model of atherosclerosis. When fed with 2% cholesterol for 17 weeks, only the wild-type mice exhibited significantly increased APP695 (123%) and APP770 (138%) mRNA levels in the cortex. The HC diet-induced hypercholesterolemia significantly increased the APP isoform levels in the membrane-bound fraction, not only in the wild-type animals (114%), but also in the Tg apoB(+/+) group (171%). The overexpression of human apoB-100 gene by the liver alone reduced the brain APP isoform levels in the membrane-bound fraction (78%), whereas the levels were increased by the combined effect of HC and the overexpression of the human apoB-100 gene (134%). The protein kinase C and beta-secretase protein levels were not altered by the individual or combined effects of these two factors. Our data indicate that the two atherogenic factors, the HC diet and the overexpression of the human apoB-100 gene by the liver, could exert different effects on the processing and expression of APP in the mice brain.

• Authors: Annamária Bjelik, Erika Bereczki, Szilvia Gonda, Anna Juhász, Agnes Rimanóczy, Marianna Zana, Tamás Csont, Magdolna Pákáski, Krisztina Boda, Péter Ferdinandy, László Dux, Zoltán Janka, Miklós Sántha, János Kálmán
• Journal: Neurochemistry international (Neurochem Int) Vol. 49 Issue 4 Pg. 393-400 (Sep 2006) ISSN: 0197-0186 [Print] England
• PMID: 16546298 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Protein Precursor
• Apolipoproteins B
• Cholesterol, Dietary
• DNA Primers
• Lipids
• Cholesterol
• Protein Kinase C
• Amyloid Precursor Protein Secretases
• Endopeptidases
• Aspartic Acid Endopeptidases
• BACE1 protein, human
• Bace1 protein, mouse

Topics

• Amyloid Precursor Protein Secretases
• Amyloid beta-Protein Precursor (metabolism)
• Animals
• Apolipoproteins B (biosynthesis, genetics)
• Aspartic Acid Endopeptidases
• Atherosclerosis (genetics, metabolism)
• Blotting, Western
• Brain Chemistry (drug effects)
• Cholesterol (blood)
• Cholesterol, Dietary (pharmacology)
• DNA Primers
• Diet
• Endopeptidases (metabolism)
• Female
• Lipids (blood)
• Mice
• Mice, Inbred C57BL
• Mice, Inbred CBA
• Mice, Transgenic
• Protein Kinase C (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction