CYP46A1 and the APOEε4 Allele Polymorphisms Correlate with the Risk of Alzheimer’s Disease

Polymorphisms of the cholesterol-24S-hydroxylase ( CYP46A1 ) and apolipoprotein E ( APOE ) genes are risk factors for Alzheimer’s disease (AD). Plasma level of 24S-hydroxcholesterol (24-OHC), the metabolite of cholesterol, is thought to correlate with AD. The present study investigated the correlati...

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Bibliographic Details
Published in:Molecular neurobiology 2018-10, Vol.55 (10), p.8179-8187
Main Authors: Li, Ling, Zeng, Fan, Liu, Yu-Hui, Li, Hui-Yun, Dong, Shu-Yang, Peng, Ze-Yan, Wang, Yan-Jiang, Zhou, Hua-Dong
Format: Article
Language:English
Subjects:
Aged
Alleles
Alzheimer Disease - blood
Alzheimer Disease - genetics
Alzheimer's disease
Amyloid beta-Peptides - blood
Apolipoprotein E
Apolipoproteins E - genetics
Association analysis
Biomedical and Life Sciences
Biomedicine
Blood
Case-Control Studies
Cell Biology
Cholesterol
Cholesterol 24-Hydroxylase - genetics
Demography
Female
Genetic Association Studies
Genetic factors
Genetic Predisposition to Disease
Genotypes
Health risk assessment
Health risks
Humans
Hydroxycholesterols - blood
Hydroxylase
Male
Neurobiology
Neurology
Neurosciences
Polymorphism, Single Nucleotide - genetics
Risk Factors
Severity of Illness Index
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Summary:Polymorphisms of the cholesterol-24S-hydroxylase ( CYP46A1 ) and apolipoprotein E ( APOE ) genes are risk factors for Alzheimer’s disease (AD). Plasma level of 24S-hydroxcholesterol (24-OHC), the metabolite of cholesterol, is thought to correlate with AD. The present study investigated the correlation between these genetic factors and blood 24-OHC and amyloid-beta (Aβ) levels in AD patients. Association analysis, logistic regression, and linear regression were used to analyze the correlation of CYP46A1 and APOE genotypes with blood 24-OHC and Aβ levels and AD risk. We found that the APOEε4 alleles were significantly higher in patients with AD and there was a potential synergistic interaction between the CYP46A1 C allele and APOEε4 allele in AD. Blood 24-OHC level and Aβ level were significantly higher in AD patients than controls, indicating 24-OHC could be a marker in AD diagnosis. However, AD patients with the CYP46A1 TT, but not CC, genotype had higher 24-OHC levels, which indicated that there may be other mechanisms in the relationship between CYP46A1 polymorphisms and AD.
ISSN:0893-7648
1559-1182
DOI:10.1007/s12035-018-0952-9