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Cholesteryl ester transfer protein (CETP) polymorphism modifies the Alzheimer's disease risk associated with APOE ε4 allele
Abstract
Cholesterol regulates the production of amyloid beta (Abeta), which is central to the pathogenesis of Alzheimer's disease (AD), with high cellular cholesterol promoting and low cellular cholesterol reducing Abeta in vitro and in vivo. High density lipoprotein (HDL) plays a central role in the removal of excess cholesterol from cells, and cholesteryl ester transfer protein (CETP) is a crucial protein involved in the regulation of HDL levels. Two common polymorphisms in the promoter region (C-629A) and exon 14 I405V of the CETP gene are associated with CETP activity and HDL levels. To investigate if these sequence variants in CETP might be of importance in mediating susceptibility to AD, independently or in concert with apolipoprotein E (APOE) epsilon4 allele, we studied a sample of 286 Spanish AD patients and 315 healthy controls. In APOE epsilon4 carriers, homozygous for the CETP (-629) A allele had approximately a three times lower risk of developing AD (odds ratio 2.33, 95% CI 1.01-5.37), than homozygous and heterozygous carriers of the CETP (-629) C allele (odds ratio 7.12, 95% CI 4.51-11.24, P for APOE epsilon4/CETP (-629) AA genotype interaction < 0.001). Our data suggest that CETP behaves as a modifier gene of the AD risk associated with the APOE epsilon4 allele, possibly through modulation of brain cholesterol metabolism.
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When assessing AD risk associated with the ApoE4 allele, CETP polymorphisms such as the C-629 A and Taq1B polymorphisms are associated with decreased AD risk.
“However, when assessing AD risk associated with the ApoE4 allele, CETP polymorphisms such as the C-629 A and Taq1B polymorphisms are associated with decreased AD risk [80, 81].”
From ApoE lipoproteins in the central nervous system under homeostasis and role in Alzheimer’s disease and related disorders (2026) · cites this paper as [81]
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Genetic Determinants of Human Health Span and Life Span: Progress and New Opportunities
Martin, G. M., Bergman, A., & Barzilai, N. (2007) · PLoS Genetics · doi:10.1371/journal.pgen.0030125 · Cited by 120
High-density lipoprotein-related cholesterol metabolism in Alzheimer's disease
Pedrini, S., Chatterjee, P., Hone, E., & Martins, R. N. (2021) · Journal of Neurochemistry · doi:10.1111/jnc.15170 · Cited by 22
Strickland, M. R., & Holtzman, D. M. (2026) · Molecular Neurodegeneration · doi:10.1186/s13024-026-00970-0
Metadata
- Authors
- Rodríguez, E., Mateo, I., Infante, J., Llorca, J., Berciano, J., & Combarros, O.
- Venue
- Journal of Neurology
- Published
- 2005-08-17
- Volume
- 253
- Issue
- 2
- Pages
- 181-185
- ISSN
- 0340-5354
- 1432-1459
- Cited by
- 47
- References
- 1
- Language
- en
- Licence
- www.springer.com/tdm (tdm)
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