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Superior Frontal Gyrus TOMM40-APOE Locus DNA Methylation in Alzheimer’s Disease
- Source :
- Bezuch, N, Bradburn, S, Robinson, A, Pendleton, N, Payton, A & Murgatroyd, C 2021, ' Superior Frontal Gyrus TOMM40-APOE Locus DNA Methylation in Alzheimer’s Disease ', Journal of Alzheimer's Disease Reports, vol. 5, no. 1, pp. 275-282 . https://doi.org/10.3233/ADR-201000, Journal of Alzheimer's Disease Reports
- Publication Year :
- 2021
- Publisher :
- IOS Press, 2021.
-
Abstract
- Background: The APOE ɛ4 allele is the strongest known genetic risk factor for sporadic Alzheimer’s disease (AD). The neighboring TOMM40 gene has also been implicated in AD due to its close proximity to APOE. Objective: Here we tested whether methylation of the TOMM40-APOE locus may influence ApoE protein levels and AD pathology. Methods: DNA methylation levels across the TOMM40-APOE locus and ApoE levels were measured in superior frontal gyrus tissues of 62 human brains genotyped for APOE and scored for AD neuropathology. Results: Methylation levels within the TOMM40 CpG island in the promoter or APOE CpG island in Exon 4 did not differ between APOE ɛ4 carriers versus non-carriers. However, APOE ɛ4 carriers had significantly higher methylation the APOE promoter compared with non-carriers. Although DNA methylation at TOMM40, APOE promoter region, or APOE did not differ between AD pathological groups, there was a negative association between TOMM40 methylation and CERAD scores. ApoE protein concentrations did not significantly different between APOE ɛ4 carriers and non-carriers, or between AD pathological groups. Finally, there was no correlation between ApoE protein concentrations and DNA methylation levels. Conclusion: APOE gene methylation may not be affected by genotype, relate to AD pathology or ApoE protein levels in the superior frontal gyrus, though, DNA methylation at the ApoE promoter differed between genotype. DNA methylation at TOMM40 associated with amyloid-β plaques and longitudinal fluid intelligence. In sum, these results suggest a complicated regulation of the TOMM40-APOE locus in the brain in controlling ApoE protein levels and AD neuropathology.
- Subjects :
- 0301 basic medicine
Apolipoprotein E
Research Report
medicine.medical_specialty
Locus (genetics)
Biology
TOMM40
03 medical and health sciences
0302 clinical medicine
frontal gyrus
Internal medicine
medicine
Allele
neuropathology
DNA methylation
General Neuroscience
Promoter
Methylation
Alzheimer's disease
Psychiatry and Mental health
Clinical Psychology
030104 developmental biology
Endocrinology
CpG site
Superior frontal gyrus
lipids (amino acids, peptides, and proteins)
Geriatrics and Gerontology
Alzheimer’s disease
030217 neurology & neurosurgery
APOE
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Bezuch, N, Bradburn, S, Robinson, A, Pendleton, N, Payton, A & Murgatroyd, C 2021, ' Superior Frontal Gyrus TOMM40-APOE Locus DNA Methylation in Alzheimer’s Disease ', Journal of Alzheimer's Disease Reports, vol. 5, no. 1, pp. 275-282 . https://doi.org/10.3233/ADR-201000, Journal of Alzheimer's Disease Reports
- Accession number :
- edsair.doi.dedup.....2beea344bef592d7e0a098daf006334e
- Full Text :
- https://doi.org/10.3233/ADR-201000