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

Annamária Bjelik, Erika Bereczki, Szilvia Gonda, A. Juhász, A. Rimanóczy, Marianna Zana, T. Csont, M. Pákáski, K. Boda, P. Ferdinándy, L. Dux, Z. Janka, M. Sántha, J. Kálmán

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Abstract

Epidemiological and biochemical data suggest a link between the cholesterol metabolism, the amyloid precursor protein (APP) processing and the increased cerebral β-amyloid (Aβ) 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 β-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.

Original languageEnglish
Pages (from-to)393-400
Number of pages8
JournalNeurochemistry International
Volume49
Issue number4
DOIs
Publication statusPublished - Sep 2006

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Amyloid beta-Protein Precursor
Apolipoprotein B-100
Apolipoproteins B
Transgenic Mice
Atherosclerosis
Cholesterol
Diet
Brain
Amyloid
Genes
Protein Isoforms
Amyloid Precursor Protein Secretases
Wild Animals
Membranes
Liver
Hypercholesterolemia
Protein Kinase C
Alzheimer Disease
Messenger RNA
Proteins

Keywords

  • Alzheimer's disease
  • Amyloid precursor protein
  • ApoB-100
  • Brain
  • Cholesterol
  • mRNA
  • Transgenic mice

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

@article{127f8dae61014abaab87071cac8a2cea,
title = "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 β-amyloid (Aβ) 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 β-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.",
keywords = "Alzheimer's disease, Amyloid precursor protein, ApoB-100, Brain, Cholesterol, mRNA, Transgenic mice",
author = "Annam{\'a}ria Bjelik and Erika Bereczki and Szilvia Gonda and A. Juh{\'a}sz and A. Riman{\'o}czy and Marianna Zana and T. Csont and M. P{\'a}k{\'a}ski and K. Boda and P. Ferdin{\'a}ndy and L. Dux and Z. Janka and M. S{\'a}ntha and J. K{\'a}lm{\'a}n",
year = "2006",
month = "9",
doi = "10.1016/j.neuint.2006.01.026",
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journal = "Neurochemistry International",
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TY - JOUR

T1 - Human apoB overexpression and a high-cholesterol diet differently modify the brain APP metabolism in the transgenic mouse model of atherosclerosis

AU - Bjelik, Annamária

AU - Bereczki, Erika

AU - Gonda, Szilvia

AU - Juhász, A.

AU - Rimanóczy, A.

AU - Zana, Marianna

AU - Csont, T.

AU - Pákáski, M.

AU - Boda, K.

AU - Ferdinándy, P.

AU - Dux, L.

AU - Janka, Z.

AU - Sántha, M.

AU - Kálmán, J.

PY - 2006/9

Y1 - 2006/9

N2 - Epidemiological and biochemical data suggest a link between the cholesterol metabolism, the amyloid precursor protein (APP) processing and the increased cerebral β-amyloid (Aβ) 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 β-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.

AB - Epidemiological and biochemical data suggest a link between the cholesterol metabolism, the amyloid precursor protein (APP) processing and the increased cerebral β-amyloid (Aβ) 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 β-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.

KW - Alzheimer's disease

KW - Amyloid precursor protein

KW - ApoB-100

KW - Brain

KW - Cholesterol

KW - mRNA

KW - Transgenic mice

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C2 - 16546298

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JO - Neurochemistry International

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