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Featured ArticleArticles, Neurobiology of Disease

Plant Sterols the Better Cholesterol in Alzheimer's Disease? A Mechanistical Study

Verena K. Burg, Heike S. Grimm, Tatjana L. Rothhaar, Sven Grösgen, Benjamin Hundsdörfer, Viola J. Haupenthal, Valerie C. Zimmer, Janine Mett, Oliver Weingärtner, Ulrich Laufs, Laus M. Broersen, Heikki Tanila, Tim Vanmierlo, Dieter Lütjohann, Tobias Hartmann and Marcus O.W. Grimm
Journal of Neuroscience 9 October 2013, 33 (41) 16072-16087; DOI: https://doi.org/10.1523/JNEUROSCI.1506-13.2013
Verena K. Burg
1Experimental Neurology,
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Heike S. Grimm
1Experimental Neurology,
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Tatjana L. Rothhaar
1Experimental Neurology,
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Sven Grösgen
1Experimental Neurology,
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Benjamin Hundsdörfer
1Experimental Neurology,
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Viola J. Haupenthal
1Experimental Neurology,
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Valerie C. Zimmer
1Experimental Neurology,
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Janine Mett
1Experimental Neurology,
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Oliver Weingärtner
4Clinic for Internal Medicine III, Cardiology, Angiology and Intensive-Care Medicine, Saarland University Hospital, 66421 Homburg/Saar, Germany,
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Ulrich Laufs
4Clinic for Internal Medicine III, Cardiology, Angiology and Intensive-Care Medicine, Saarland University Hospital, 66421 Homburg/Saar, Germany,
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Laus M. Broersen
5Nutricia Advanced Medical Nutrition, Danone Research, Centre of Specialised Nutrition, 6700 CA Wageningen, Netherlands,
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Heikki Tanila
6Department of Neuroscience and Neurology, University of Kuopio, 70211 Kuopio, Finland, and
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Tim Vanmierlo
7Institute of Clinical Chemistry and Clinical Pharmacology, University of Bonn, 53105 Bonn, Germany
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Dieter Lütjohann
7Institute of Clinical Chemistry and Clinical Pharmacology, University of Bonn, 53105 Bonn, Germany
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Tobias Hartmann
1Experimental Neurology,
2Deutsches Institut für DemenzPrävention (DIDP), and
3Neurodegeneration and Neurobiology, Saarland University, and
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Marcus O.W. Grimm
1Experimental Neurology,
2Deutsches Institut für DemenzPrävention (DIDP), and
3Neurodegeneration and Neurobiology, Saarland University, and
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Abstract

Amyloid-β (Aβ), major constituent of senile plaques in Alzheimer's disease (AD), is generated by proteolytic processing of the amyloid precursor protein (APP) by β- and γ-secretase. Several lipids, especially cholesterol, are associated with AD. Phytosterols are naturally occurring cholesterol plant equivalents, recently been shown to cross the blood–brain-barrier accumulating in brain. Here, we investigated the effect of the most nutritional prevalent phytosterols and cholesterol on APP processing. In general, phytosterols are less amyloidogenic than cholesterol. However, only one phytosterol, stigmasterol, reduced Aβ generation by (1) directly decreasing β-secretase activity, (2) reducing expression of all γ-secretase components, (3) reducing cholesterol and presenilin distribution in lipid rafts implicated in amyloidogenic APP cleavage, and by (4) decreasing BACE1 internalization to endosomal compartments, involved in APP β-secretase cleavage. Mice fed with stigmasterol-enriched diets confirmed protective effects in vivo, suggesting that dietary intake of phytosterol blends mainly containing stigmasterol might be beneficial in preventing AD.

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The Journal of Neuroscience: 33 (41)
Journal of Neuroscience
Vol. 33, Issue 41
9 Oct 2013
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Plant Sterols the Better Cholesterol in Alzheimer's Disease? A Mechanistical Study
Verena K. Burg, Heike S. Grimm, Tatjana L. Rothhaar, Sven Grösgen, Benjamin Hundsdörfer, Viola J. Haupenthal, Valerie C. Zimmer, Janine Mett, Oliver Weingärtner, Ulrich Laufs, Laus M. Broersen, Heikki Tanila, Tim Vanmierlo, Dieter Lütjohann, Tobias Hartmann, Marcus O.W. Grimm
Journal of Neuroscience 9 October 2013, 33 (41) 16072-16087; DOI: 10.1523/JNEUROSCI.1506-13.2013

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Plant Sterols the Better Cholesterol in Alzheimer's Disease? A Mechanistical Study
Verena K. Burg, Heike S. Grimm, Tatjana L. Rothhaar, Sven Grösgen, Benjamin Hundsdörfer, Viola J. Haupenthal, Valerie C. Zimmer, Janine Mett, Oliver Weingärtner, Ulrich Laufs, Laus M. Broersen, Heikki Tanila, Tim Vanmierlo, Dieter Lütjohann, Tobias Hartmann, Marcus O.W. Grimm
Journal of Neuroscience 9 October 2013, 33 (41) 16072-16087; DOI: 10.1523/JNEUROSCI.1506-13.2013
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