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SREBP-1a Polymorphism Influences the Risk of Alzheimer’s Disease in Carriers of the ApoE4 Allele

Sterol regulatory element-binding proteins (SREBPs) are transcription factors involved in cholesterol and fatty acid synthesis. Recently, a polymorphism in the 5′-region of the SREBP-1a gene has been described to be correlated with alterations in the plasma levels of cholesterol. Consequently the re...

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Main Authors: Spell, Christian (Author) , Kölsch, Heike (Author) , Lütjohann, Dieter (Author) , Kerksiek, Anja (Author) , Hentschel, Frank (Author) , Damian, Marinella (Author) , Bergmann, Klaus von (Author) , Rao, Marie Luise (Author) , Maier, Wolfgang (Author) , Heun, Reinhard (Author)
Format: Article (Journal)
Language:English
Published: October 2004
In: Dementia and geriatric cognitive disorders
Year: 2004, Volume: 18, Issue: 3/4, Pages: 245-249
ISSN:1421-9824
DOI:10.1159/000080023
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1159/000080023
Verlag, lizenzpflichtig, Volltext: https://www.karger.com/Article/FullText/80023
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Author Notes:Christian Spell, Heike Kölsch, Dieter Lütjohann, Anja Kerksiek, Frank Hentschel, Marinella Damian, Klaus von Bergmann, Marie Luise Rao, Wolfgang Maier, Reinhard Heun
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Summary:Sterol regulatory element-binding proteins (SREBPs) are transcription factors involved in cholesterol and fatty acid synthesis. Recently, a polymorphism in the 5′-region of the SREBP-1a gene has been described to be correlated with alterations in the plasma levels of cholesterol. Consequently the relationship between this SREBP-1a gene polymorphism and Alzheimer’s disease (AD) alone and in combination with the apolipoprotein E (ApoE) 4 allele was evaluated. No association between SREBP-1a polymorphism alone and AD could be seen. However, in the group of healthy ApoE4 allele carriers, the number of homozygote SREBP-1a ΔG allele carriers was significantly higher than in AD patients. Cerebrospinal fluid levels of cholesterol were lower in AD patients who were carriers of the SREBP-1a ΔG allele, and the ratio of 24S-hydroxycholesterol to cholesterol was increased in these probands. Our data suggest a reduced risk of AD in carriers of an ApoE4 allele who are additionally homozygous for the SREBP-1a ΔG allele, which is possibly due to the influence of SREBP-1a polymorphism on brain cholesterol metabolism. This is the first report on a genetic factor which prevents the deleterious effect of the ApoE4 allele and thus reduces the risk of AD.
Item Description:Gesehen am 11.11.2020
Physical Description:Online Resource
ISSN:1421-9824
DOI:10.1159/000080023

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