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Apolipoprotein E genotype and alpha‐tocopherol modulate amyloid precursor protein metabolism and cell cycle regulation
Author(s) -
Huebbe Patricia,
Schaffer Sebastian,
JofreMonseny Laia,
BoeschSaadatmandi Christine,
Minihane AnneMarie,
Müller Walter E.,
Eckert Gunter P.,
Rimbach Gerald
Publication year - 2007
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.200700194
Subject(s) - apolipoprotein e , endocrinology , medicine , amyloid precursor protein , biology , apolipoprotein b , cholesterol , genotype , chemistry , biochemistry , alzheimer's disease , gene , disease
Apolipoprotein E4 (apoE4) genotype is associated with an increased risk for Alzheimer's disease (AD). This is thought to be in part attributable to an impact of apoE genotype on the processing of the transmembrane amyloid precursor protein (APP) thereby contributing to amyloid beta peptide formation in apoE4 carriers, which is a primary patho‐physiological feature of AD. As apoE and alpha‐tocopherol (α‐toc) have been shown to modulate membrane bilayer properties and hippocampal gene expression, we studied the effect of apoE genotype on APP metabolism and cell cycle regulation in response to dietary α‐toc. ApoE3 and apoE4 transgenic mice were fed a diet low (VE) or high (+VE) in vitamin E (3 and 235 mg α‐toc/kg diet, respectively) for 12 weeks. Cholesterol levels and membrane fluidity were not different in synaptosomal plasma membranes isolated from brains of apoE3 and apoE4 mice (–VE and +VE). Non‐amyloidogenic alpha‐secretase mRNA concentration and activity were significantly higher in brains of apoE3 relative to apoE4 mice irrespective of the dietary α‐toc supply, while amyloidogenic beta‐secretase and gamma‐secretase remained unchanged. Relative mRNA concentration of cell cycle related proteins were modulated differentially by dietary α‐toc supplementation in apoE3 and apoE4 mice, suggesting genotype‐dependent signalling effects on cell cycle regulation.