1. SREBP-1a Polymorphism Influences the Risk of Alzheimer’s Disease in Carriers of the ApoE4 Allele
- Author
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Marie Luise Rao, Christian Spell, Wolfgang Maier, Reinhard Heun, Frank Hentschel, Klaus von Bergmann, Anja Kerksiek, Dieter Lütjohann, Heike Kölsch, and Marinella Damian
- Subjects
Male ,Apolipoprotein E ,Receptors, Steroid ,medicine.medical_specialty ,Apolipoprotein B ,Cognitive Neuroscience ,Apolipoprotein E4 ,Polymerase Chain Reaction ,digestive system ,chemistry.chemical_compound ,Apolipoproteins E ,Gene Frequency ,Alzheimer Disease ,Internal medicine ,polycyclic compounds ,medicine ,Humans ,Genetic Predisposition to Disease ,Allele ,Alleles ,Aged ,DNA Primers ,Aged, 80 and over ,Polymorphism, Genetic ,biology ,Cholesterol ,Genetic Carrier Screening ,Homozygote ,Brain ,food and beverages ,medicine.disease ,Hydroxycholesterols ,Sterol ,Sterol regulatory element-binding protein ,DNA-Binding Proteins ,Psychiatry and Mental health ,Endocrinology ,chemistry ,CCAAT-Enhancer-Binding Proteins ,biology.protein ,Female ,lipids (amino acids, peptides, and proteins) ,Gene polymorphism ,Geriatrics and Gerontology ,Alzheimer's disease ,Sterol Regulatory Element Binding Protein 1 ,Transcription Factors - 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.
- Published
- 2004
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