Cholesterol depletion reduces aggregation of amyloid-beta peptide in hippocampal neurons

A key event in the pathogenesis of Alzheimer's disease is the conversion of soluble amyloid Aβ-peptide into toxic aggregates. Here, we studied the effect of cholesterol depletion on the formation of insoluble Aβ. We found that reduction of neuronal cholesterol by ∼25% reduced the neuronal forma...

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Main Authors: Anja Schneider, Walter Schulz-Schaeffer, Tobias Hartmann, Jörg B. Schulz, Mikael Simons
Format: Article
Language:English
Published: Elsevier 2006-09-01
Series:Neurobiology of Disease
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S096999610600101X
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spelling doaj-dd279bf64a91425f80baac8f61c0e9362021-03-20T04:52:56ZengElsevierNeurobiology of Disease1095-953X2006-09-01233573577Cholesterol depletion reduces aggregation of amyloid-beta peptide in hippocampal neuronsAnja Schneider0Walter Schulz-Schaeffer1Tobias Hartmann2Jörg B. Schulz3Mikael Simons4Center for Biochemistry and Molecular Cell Biology, University of Göttingen, Humboldtallee 23, 37073 Göttingen, GermanyDepartment of Neuropathology, University of Göttingen, Robert-Koch-Str. 40, 37099 Göttingen, GermanyCenter for Molecular Biology (ZMBH), Im Neuenheimer Feld 282, 69120 Heidelberg, GermanyDepartment of Neurodegeneration and Restorative Research, Center of NeurologicalMedicine and CMPB, Waldweg 33, 37073 Göttingen, GermanyCenter for Biochemistry and Molecular Cell Biology, University of Göttingen, Humboldtallee 23, 37073 Göttingen, Germany; Corresponding author. Fax: +49 551 3899201.A key event in the pathogenesis of Alzheimer's disease is the conversion of soluble amyloid Aβ-peptide into toxic aggregates. Here, we studied the effect of cholesterol depletion on the formation of insoluble Aβ. We found that reduction of neuronal cholesterol by ∼25% reduced the neuronal formation of insoluble Aβ without affecting the secretion of soluble Aβ. Moreover, we demonstrate that Aβ-oligomers from Alzheimer's disease brains associate with a detergent-resistant membrane fraction in a cholesterol-dependent manner. These results suggest a key role for cholesterol in aggregation of Aβ.http://www.sciencedirect.com/science/article/pii/S096999610600101XCholesterolAggregationHippocampal neuronsAβOligomersAlzheimer's disease
collection DOAJ
language English
format Article
sources DOAJ
author Anja Schneider
Walter Schulz-Schaeffer
Tobias Hartmann
Jörg B. Schulz
Mikael Simons
spellingShingle Anja Schneider
Walter Schulz-Schaeffer
Tobias Hartmann
Jörg B. Schulz
Mikael Simons
Cholesterol depletion reduces aggregation of amyloid-beta peptide in hippocampal neurons
Neurobiology of Disease
Cholesterol
Aggregation
Hippocampal neurons

Oligomers
Alzheimer's disease
author_facet Anja Schneider
Walter Schulz-Schaeffer
Tobias Hartmann
Jörg B. Schulz
Mikael Simons
author_sort Anja Schneider
title Cholesterol depletion reduces aggregation of amyloid-beta peptide in hippocampal neurons
title_short Cholesterol depletion reduces aggregation of amyloid-beta peptide in hippocampal neurons
title_full Cholesterol depletion reduces aggregation of amyloid-beta peptide in hippocampal neurons
title_fullStr Cholesterol depletion reduces aggregation of amyloid-beta peptide in hippocampal neurons
title_full_unstemmed Cholesterol depletion reduces aggregation of amyloid-beta peptide in hippocampal neurons
title_sort cholesterol depletion reduces aggregation of amyloid-beta peptide in hippocampal neurons
publisher Elsevier
series Neurobiology of Disease
issn 1095-953X
publishDate 2006-09-01
description A key event in the pathogenesis of Alzheimer's disease is the conversion of soluble amyloid Aβ-peptide into toxic aggregates. Here, we studied the effect of cholesterol depletion on the formation of insoluble Aβ. We found that reduction of neuronal cholesterol by ∼25% reduced the neuronal formation of insoluble Aβ without affecting the secretion of soluble Aβ. Moreover, we demonstrate that Aβ-oligomers from Alzheimer's disease brains associate with a detergent-resistant membrane fraction in a cholesterol-dependent manner. These results suggest a key role for cholesterol in aggregation of Aβ.
topic Cholesterol
Aggregation
Hippocampal neurons

Oligomers
Alzheimer's disease
url http://www.sciencedirect.com/science/article/pii/S096999610600101X
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AT tobiashartmann cholesteroldepletionreducesaggregationofamyloidbetapeptideinhippocampalneurons
AT jorgbschulz cholesteroldepletionreducesaggregationofamyloidbetapeptideinhippocampalneurons
AT mikaelsimons cholesteroldepletionreducesaggregationofamyloidbetapeptideinhippocampalneurons
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