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

• Verfasst von: Spell, Christian [VerfasserIn]
• Verfasst von: Kölsch, Heike [VerfasserIn]
• Verfasst von: Lütjohann, Dieter [VerfasserIn]
• Verfasst von: Kerksiek, Anja [VerfasserIn]
• Verfasst von: Hentschel, Frank [VerfasserIn]
• Verfasst von: Damian, Marinella [VerfasserIn]
• Verfasst von: Bergmann, Klaus von [VerfasserIn]
• Verfasst von: Rao, Marie Luise [VerfasserIn]
• Verfasst von: Maier, Wolfgang [VerfasserIn]
• Verfasst von: Heun, Reinhard [VerfasserIn]
• Titel: SREBP-1a Polymorphism Influences the Risk of Alzheimer’s Disease in Carriers of the ApoE4 Allele
• Verf.angabe: Christian Spell, Heike Kölsch, Dieter Lütjohann, Anja Kerksiek, Frank Hentschel, Marinella Damian, Klaus von Bergmann, Marie Luise Rao, Wolfgang Maier, Reinhard Heun
• E-Jahr: 2004
• Jahr: October 2004
• Umfang: 5 S.
• Fussnoten: Gesehen am 11.11.2020
• Titel Quelle: Enthalten in: Dementia and geriatric cognitive disorders
• Ort Quelle: Basel : Karger, 1998
• Jahr Quelle: 2004
• Band/Heft Quelle: 18(2004), 3/4, Seite 245-249
• ISSN Quelle: 1421-9824
• DOI: doi:10.1159/000080023
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1738422372

Abstract

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.