Journal
DEMENTIA AND GERIATRIC COGNITIVE DISORDERS
Volume 18, Issue 3-4, Pages 245-249Publisher
KARGER
DOI: 10.1159/000080023
Keywords
sterol regulatory element-binding protein; Alzheimer's disease; apolipoprotein E4; association; interaction; brain cholesterol; 24S-hydroxycholesterol; polymorphism; cerebrospinal fluid; brain; oxysterols
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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 DeltaG 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 DeltaG 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 DeltaG 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. Copyright (C) 2004 S. Karger AG, Basel.
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