Plasmalogens Inhibit APP Processing by Directly Affecting γ-Secretase Activity in Alzheimer’s Disease
Lipids play an important role as risk or protective factors in Alzheimer’s disease (AD). Previously it has been shown that plasmalogens, the major brain phospholipids, are altered in AD. However, it remained unclear whether plasmalogens themselves are able to modulate amyloid precursor protein (APP)...
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| Language: | English |
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Wiley
2012-01-01
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| Series: | The Scientific World Journal |
| Online Access: | http://dx.doi.org/10.1100/2012/141240 |
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| author | Tatjana L. Rothhaar Sven Grösgen Viola J. Haupenthal Verena K. Burg Benjamin Hundsdörfer Janine Mett Matthias Riemenschneider Heike S. Grimm Tobias Hartmann Marcus O. W. Grimm |
| author_facet | Tatjana L. Rothhaar Sven Grösgen Viola J. Haupenthal Verena K. Burg Benjamin Hundsdörfer Janine Mett Matthias Riemenschneider Heike S. Grimm Tobias Hartmann Marcus O. W. Grimm |
| author_sort | Tatjana L. Rothhaar |
| collection | DOAJ |
| description | Lipids play an important role as risk or protective factors in Alzheimer’s disease (AD). Previously it has been shown that plasmalogens, the major brain phospholipids, are altered in AD. However, it remained unclear whether plasmalogens themselves are able to modulate amyloid precursor protein (APP) processing or if the reduced plasmalogen level is a consequence of AD. Here we identify the plasmalogens which are altered in human AD postmortem brains and investigate their impact on APP processing resulting in Aβ production. All tested plasmalogen species showed a reduction in γ-secretase activity whereas β- and α-secretase activity mainly remained unchanged. Plasmalogens directly affected γ-secretase activity, protein and RNA level of the secretases were unaffected, pointing towards a direct influence of plasmalogens on γ-secretase activity. Plasmalogens were also able to decrease γ-secretase activity in human postmortem AD brains emphasizing the impact of plasmalogens in AD. In summary our findings show that decreased plasmalogen levels are not only a consequence of AD but that plasmalogens also decrease APP processing by directly affecting γ-secretase activity, resulting in a vicious cycle: Aβ reduces plasmalogen levels and reduced plasmalogen levels directly increase γ-secretase activity leading to an even stronger production of Aβ peptides. |
| format | Article |
| id | doaj-art-98aa520ca5ca49378dbdfeb1c8c2fa22 |
| institution | Kabale University |
| issn | 1537-744X |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | The Scientific World Journal |
| spelling | doaj-art-98aa520ca5ca49378dbdfeb1c8c2fa222025-08-20T03:37:22ZengWileyThe Scientific World Journal1537-744X2012-01-01201210.1100/2012/141240141240Plasmalogens Inhibit APP Processing by Directly Affecting γ-Secretase Activity in Alzheimer’s DiseaseTatjana L. Rothhaar0Sven Grösgen1Viola J. Haupenthal2Verena K. Burg3Benjamin Hundsdörfer4Janine Mett5Matthias Riemenschneider6Heike S. Grimm7Tobias Hartmann8Marcus O. W. Grimm9Experimental Neurology, Saarland University, Kirrbergerstraβe, 66421 Homburg/Saar, GermanyExperimental Neurology, Saarland University, Kirrbergerstraβe, 66421 Homburg/Saar, GermanyExperimental Neurology, Saarland University, Kirrbergerstraβe, 66421 Homburg/Saar, GermanyExperimental Neurology, Saarland University, Kirrbergerstraβe, 66421 Homburg/Saar, GermanyExperimental Neurology, Saarland University, Kirrbergerstraβe, 66421 Homburg/Saar, GermanyExperimental Neurology, Saarland University, Kirrbergerstraβe, 66421 Homburg/Saar, GermanyPsychiatry, Saarland University, Kirrbergerstraβe, 66421 Homburg/Saar, GermanyExperimental Neurology, Saarland University, Kirrbergerstraβe, 66421 Homburg/Saar, GermanyExperimental Neurology, Saarland University, Kirrbergerstraβe, 66421 Homburg/Saar, GermanyExperimental Neurology, Saarland University, Kirrbergerstraβe, 66421 Homburg/Saar, GermanyLipids play an important role as risk or protective factors in Alzheimer’s disease (AD). Previously it has been shown that plasmalogens, the major brain phospholipids, are altered in AD. However, it remained unclear whether plasmalogens themselves are able to modulate amyloid precursor protein (APP) processing or if the reduced plasmalogen level is a consequence of AD. Here we identify the plasmalogens which are altered in human AD postmortem brains and investigate their impact on APP processing resulting in Aβ production. All tested plasmalogen species showed a reduction in γ-secretase activity whereas β- and α-secretase activity mainly remained unchanged. Plasmalogens directly affected γ-secretase activity, protein and RNA level of the secretases were unaffected, pointing towards a direct influence of plasmalogens on γ-secretase activity. Plasmalogens were also able to decrease γ-secretase activity in human postmortem AD brains emphasizing the impact of plasmalogens in AD. In summary our findings show that decreased plasmalogen levels are not only a consequence of AD but that plasmalogens also decrease APP processing by directly affecting γ-secretase activity, resulting in a vicious cycle: Aβ reduces plasmalogen levels and reduced plasmalogen levels directly increase γ-secretase activity leading to an even stronger production of Aβ peptides.http://dx.doi.org/10.1100/2012/141240 |
| spellingShingle | Tatjana L. Rothhaar Sven Grösgen Viola J. Haupenthal Verena K. Burg Benjamin Hundsdörfer Janine Mett Matthias Riemenschneider Heike S. Grimm Tobias Hartmann Marcus O. W. Grimm Plasmalogens Inhibit APP Processing by Directly Affecting γ-Secretase Activity in Alzheimer’s Disease The Scientific World Journal |
| title | Plasmalogens Inhibit APP Processing by Directly Affecting γ-Secretase Activity in Alzheimer’s Disease |
| title_full | Plasmalogens Inhibit APP Processing by Directly Affecting γ-Secretase Activity in Alzheimer’s Disease |
| title_fullStr | Plasmalogens Inhibit APP Processing by Directly Affecting γ-Secretase Activity in Alzheimer’s Disease |
| title_full_unstemmed | Plasmalogens Inhibit APP Processing by Directly Affecting γ-Secretase Activity in Alzheimer’s Disease |
| title_short | Plasmalogens Inhibit APP Processing by Directly Affecting γ-Secretase Activity in Alzheimer’s Disease |
| title_sort | plasmalogens inhibit app processing by directly affecting γ secretase activity in alzheimer s disease |
| url | http://dx.doi.org/10.1100/2012/141240 |
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