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