Increased Brain β-Amyloid Load, Phosphorylated Tau, and Risk of Alzheimer Disease Associated With an Intronic CYP46 Polymorphism

Abstract

CYP46 influences brain beta-amyloid load, cerebrospinal fluid levels of beta-amyloid peptides and phosphorylated tau, and the genetic risk of late-onset sporadic AD.

Polymorphism in the Cholesterol 24S-Hydroxylase Gene (CYP46A1) Associated with the APOEυ3 Allele Increases the Risk of Alzheimer’s Disease and of Mild Cognitive Impairment Progressing to Alzheimer’s Disease

“…In the same way, the analysis of 23 patients initially diagnosed as having MCI that developed into AD during the study revealed an increase in the frequency of the CYP46A1-T allele associated with APOE 3. These results differ from those obtained by Papassotiropoulos et al [18] in that they do not show a synergy between the alleles CYP46A1-T and APOE 4. One possible cause for the controversy found between the results obtained by Papassotiropoulos et al [18] and the ones obtained in this study may be an erroneous genotyping.…”

“…These results differ from those obtained by Papassotiropoulos et al [18] in that they do not show a synergy between the alleles CYP46A1-T and APOE 4. One possible cause for the controversy found between the results obtained by Papassotiropoulos et al [18] and the ones obtained in this study may be an erroneous genotyping. This explanation has been discarded for two reasons: (a) the studied samples are in Hardy-Weinberg equilibrium and (b) the genotype has been verifi ed using a second restriction enzyme.…”

Polymorphism in the Cholesterol 24S-Hydroxylase Gene (CYP46A1) Associated with the APOEυ3 Allele Increases the Risk of Alzheimer’s Disease and of Mild Cognitive Impairment Progressing to Alzheimer’s Disease

“…In the same way, the analysis of 23 patients initially diagnosed as having MCI that developed into AD during the study revealed an increase in the frequency of the CYP46A1-T allele associated with APOE 3. These results differ from those obtained by Papassotiropoulos et al [18] in that they do not show a synergy between the alleles CYP46A1-T and APOE 4. One possible cause for the controversy found between the results obtained by Papassotiropoulos et al [18] and the ones obtained in this study may be an erroneous genotyping.…”

“…These results differ from those obtained by Papassotiropoulos et al [18] in that they do not show a synergy between the alleles CYP46A1-T and APOE 4. One possible cause for the controversy found between the results obtained by Papassotiropoulos et al [18] and the ones obtained in this study may be an erroneous genotyping. This explanation has been discarded for two reasons: (a) the studied samples are in Hardy-Weinberg equilibrium and (b) the genotype has been verifi ed using a second restriction enzyme.…”

Variants of CYP46A1 may interact with age and APOE to influence CSF A�42 levels in Alzheimer?s disease

“…In agreement with the results of Papassotiropoulos et al (2003), evidence has been obtained that rs754203 significantly influences Aβ42 levels, an effect that is exclusively evident in elderly APOE ε4 carriers in the present study. Individuals in this group with the homozygous A-allele, have higher Aβ42 concentrations in CSF than individuals with the AG or GG genotypes.…”

Genetic Association of CYP46 and Risk for Alzheimer’s Disease

“…Our findings support an independent mode of action of CYP46 C/C genotype and APOE Â4 allele in AD, and concur with the results of Papassotiropoulos et al [11]: they detected no interaction between both genes, with an OR of 2.03 for the presence of the CYP46 T/T genotype in APOE Â4-negative subjects, an OR of 4.06 for APOE Â4 carriers without the CYP46 T/T genotype, and an OR of 9.63 for the presence of both CYP46 T/T genotype and APOE Â4 allele. In conclusion, genetic variants of CYP46, or of a closely linked gene, may increase the risk of AD, independently of the APOE Â4 allele.…”

Polymorphism in the Cholesterol 24S-Hydroxylase Gene (CYP46A1) Associated with the APOEυ3 Allele Increases the Risk of Alzheimer’s Disease and of Mild Cognitive Impairment Progressing to Alzheimer’s Disease

“…In the same way, the analysis of 23 patients initially diagnosed as having MCI that developed into AD during the study revealed an increase in the frequency of the CYP46A1-T allele associated with APOE 3. These results differ from those obtained by Papassotiropoulos et al [18] in that they do not show a synergy between the alleles CYP46A1-T and APOE 4. One possible cause for the controversy found between the results obtained by Papassotiropoulos et al [18] and the ones obtained in this study may be an erroneous genotyping.…”

“…These results differ from those obtained by Papassotiropoulos et al [18] in that they do not show a synergy between the alleles CYP46A1-T and APOE 4. One possible cause for the controversy found between the results obtained by Papassotiropoulos et al [18] and the ones obtained in this study may be an erroneous genotyping. This explanation has been discarded for two reasons: (a) the studied samples are in Hardy-Weinberg equilibrium and (b) the genotype has been verifi ed using a second restriction enzyme.…”

Variants of CYP46A1 may interact with age and APOE to influence CSF A�42 levels in Alzheimer?s disease

“…In agreement with the results of Papassotiropoulos et al (2003), evidence has been obtained that rs754203 significantly influences Aβ42 levels, an effect that is exclusively evident in elderly APOE ε4 carriers in the present study. Individuals in this group with the homozygous A-allele, have higher Aβ42 concentrations in CSF than individuals with the AG or GG genotypes.…”

Genetic Association of CYP46 and Risk for Alzheimer’s Disease

“…Our findings support an independent mode of action of CYP46 C/C genotype and APOE Â4 allele in AD, and concur with the results of Papassotiropoulos et al [11]: they detected no interaction between both genes, with an OR of 2.03 for the presence of the CYP46 T/T genotype in APOE Â4-negative subjects, an OR of 4.06 for APOE Â4 carriers without the CYP46 T/T genotype, and an OR of 9.63 for the presence of both CYP46 T/T genotype and APOE Â4 allele. In conclusion, genetic variants of CYP46, or of a closely linked gene, may increase the risk of AD, independently of the APOE Â4 allele.…”

Polymorphism in the Cholesterol 24S-Hydroxylase Gene (CYP46A1) Associated with the APOEυ3 Allele Increases the Risk of Alzheimer’s Disease and of Mild Cognitive Impairment Progressing to Alzheimer’s Disease

“…In the same way, the analysis of 23 patients initially diagnosed as having MCI that developed into AD during the study revealed an increase in the frequency of the CYP46A1-T allele associated with APOE 3. These results differ from those obtained by Papassotiropoulos et al [18] in that they do not show a synergy between the alleles CYP46A1-T and APOE 4. One possible cause for the controversy found between the results obtained by Papassotiropoulos et al [18] and the ones obtained in this study may be an erroneous genotyping.…”

“…These results differ from those obtained by Papassotiropoulos et al [18] in that they do not show a synergy between the alleles CYP46A1-T and APOE 4. One possible cause for the controversy found between the results obtained by Papassotiropoulos et al [18] and the ones obtained in this study may be an erroneous genotyping. This explanation has been discarded for two reasons: (a) the studied samples are in Hardy-Weinberg equilibrium and (b) the genotype has been verifi ed using a second restriction enzyme.…”

Variants of CYP46A1 may interact with age and APOE to influence CSF A�42 levels in Alzheimer?s disease

“…In agreement with the results of Papassotiropoulos et al (2003), evidence has been obtained that rs754203 significantly influences Aβ42 levels, an effect that is exclusively evident in elderly APOE ε4 carriers in the present study. Individuals in this group with the homozygous A-allele, have higher Aβ42 concentrations in CSF than individuals with the AG or GG genotypes.…”

Genetic Association of CYP46 and Risk for Alzheimer’s Disease

“…Our findings support an independent mode of action of CYP46 C/C genotype and APOE Â4 allele in AD, and concur with the results of Papassotiropoulos et al [11]: they detected no interaction between both genes, with an OR of 2.03 for the presence of the CYP46 T/T genotype in APOE Â4-negative subjects, an OR of 4.06 for APOE Â4 carriers without the CYP46 T/T genotype, and an OR of 9.63 for the presence of both CYP46 T/T genotype and APOE Â4 allele. In conclusion, genetic variants of CYP46, or of a closely linked gene, may increase the risk of AD, independently of the APOE Â4 allele.…”