LCAT deficiency does not impair amyloid metabolism in APP/PS1 mice[S]
A key step in plasma HDL maturation from discoidal to spherical particles is the esterification of cholesterol to cholesteryl ester, which is catalyzed by LCAT. HDL-like lipoproteins in cerebrospinal fluid (CSF) are also spherical, whereas nascent lipoprotein particles secreted from astrocytes are d...
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doaj-948ef58699bc4cdaa3d7f791e46eefa82021-04-28T05:59:55ZengElsevierJournal of Lipid Research0022-22752014-08-0155817211729LCAT deficiency does not impair amyloid metabolism in APP/PS1 mice[S]Sophie Stukas0Lita Freeman1Michael Lee2Anna Wilkinson3Alice Ossoli4Boris Vaisman5Stephen Demosky6Jeniffer Chan7Veronica Hirsch-Reinshagen8Alan T. Remaley9Cheryl L. Wellington10Department of Pathology and Laboratory Medicine, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4National Institutes of Health, Bethesda, MD 20892-1508Department of Pathology and Laboratory Medicine, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4Department of Pathology and Laboratory Medicine, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4National Institutes of Health, Bethesda, MD 20892-1508National Institutes of Health, Bethesda, MD 20892-1508National Institutes of Health, Bethesda, MD 20892-1508Department of Pathology and Laboratory Medicine, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4Department of Pathology and Laboratory Medicine, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4National Institutes of Health, Bethesda, MD 20892-1508To whom correspondence should be addressed; Department of Pathology and Laboratory Medicine, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4; To whom correspondence should be addressedA key step in plasma HDL maturation from discoidal to spherical particles is the esterification of cholesterol to cholesteryl ester, which is catalyzed by LCAT. HDL-like lipoproteins in cerebrospinal fluid (CSF) are also spherical, whereas nascent lipoprotein particles secreted from astrocytes are discoidal, suggesting that LCAT may play a similar role in the CNS. In plasma, apoA-I is the main LCAT activator, while in the CNS, it is believed to be apoE. apoE is directly involved in the pathological progression of Alzheimer's disease, including facilitating β-amyloid (Aβ) clearance from the brain, a function that requires its lipidation by ABCA1. However, whether apoE particle maturation by LCAT is also required for Aβ clearance is unknown. Here we characterized the impact of LCAT deficiency on CNS lipoprotein metabolism and amyloid pathology. Deletion of LCAT from APP/PS1 mice resulted in a pronounced decrease of apoA-I in plasma that was paralleled by decreased apoA-I levels in CSF and brain tissue, whereas apoE levels were unaffected. Furthermore, LCAT deficiency did not increase Aβ or amyloid in APP/PS1 LCAT−/− mice. Finally, LCAT expression and plasma activity were unaffected by age or the onset of Alzheimer's-like pathology in APP/PS1 mice. Taken together, these results suggest that apoE-containing discoidal HDLs do not require LCAT-dependent maturation to mediate efficient Aβ clearance.http://www.sciencedirect.com/science/article/pii/S0022227520353359lecithin:cholesterol acyltransferasehigh density lipoprotein metabolismapolipoproteinsAlzheimer's disease |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sophie Stukas Lita Freeman Michael Lee Anna Wilkinson Alice Ossoli Boris Vaisman Stephen Demosky Jeniffer Chan Veronica Hirsch-Reinshagen Alan T. Remaley Cheryl L. Wellington |
spellingShingle |
Sophie Stukas Lita Freeman Michael Lee Anna Wilkinson Alice Ossoli Boris Vaisman Stephen Demosky Jeniffer Chan Veronica Hirsch-Reinshagen Alan T. Remaley Cheryl L. Wellington LCAT deficiency does not impair amyloid metabolism in APP/PS1 mice[S] Journal of Lipid Research lecithin:cholesterol acyltransferase high density lipoprotein metabolism apolipoproteins Alzheimer's disease |
author_facet |
Sophie Stukas Lita Freeman Michael Lee Anna Wilkinson Alice Ossoli Boris Vaisman Stephen Demosky Jeniffer Chan Veronica Hirsch-Reinshagen Alan T. Remaley Cheryl L. Wellington |
author_sort |
Sophie Stukas |
title |
LCAT deficiency does not impair amyloid metabolism in APP/PS1 mice[S] |
title_short |
LCAT deficiency does not impair amyloid metabolism in APP/PS1 mice[S] |
title_full |
LCAT deficiency does not impair amyloid metabolism in APP/PS1 mice[S] |
title_fullStr |
LCAT deficiency does not impair amyloid metabolism in APP/PS1 mice[S] |
title_full_unstemmed |
LCAT deficiency does not impair amyloid metabolism in APP/PS1 mice[S] |
title_sort |
lcat deficiency does not impair amyloid metabolism in app/ps1 mice[s] |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2014-08-01 |
description |
A key step in plasma HDL maturation from discoidal to spherical particles is the esterification of cholesterol to cholesteryl ester, which is catalyzed by LCAT. HDL-like lipoproteins in cerebrospinal fluid (CSF) are also spherical, whereas nascent lipoprotein particles secreted from astrocytes are discoidal, suggesting that LCAT may play a similar role in the CNS. In plasma, apoA-I is the main LCAT activator, while in the CNS, it is believed to be apoE. apoE is directly involved in the pathological progression of Alzheimer's disease, including facilitating β-amyloid (Aβ) clearance from the brain, a function that requires its lipidation by ABCA1. However, whether apoE particle maturation by LCAT is also required for Aβ clearance is unknown. Here we characterized the impact of LCAT deficiency on CNS lipoprotein metabolism and amyloid pathology. Deletion of LCAT from APP/PS1 mice resulted in a pronounced decrease of apoA-I in plasma that was paralleled by decreased apoA-I levels in CSF and brain tissue, whereas apoE levels were unaffected. Furthermore, LCAT deficiency did not increase Aβ or amyloid in APP/PS1 LCAT−/− mice. Finally, LCAT expression and plasma activity were unaffected by age or the onset of Alzheimer's-like pathology in APP/PS1 mice. Taken together, these results suggest that apoE-containing discoidal HDLs do not require LCAT-dependent maturation to mediate efficient Aβ clearance. |
topic |
lecithin:cholesterol acyltransferase high density lipoprotein metabolism apolipoproteins Alzheimer's disease |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520353359 |
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