Allelic variation within the major APOE CpG island affects its methylation in the brain of targeted replacement mice expressing human APOE

Rueter, Johanna; Rimbach, Gerald; Huebbe, Patricia

doi:10.1016/j.bbagrm.2023.194942

Cited by 1 publication

(1 citation statement)

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“…AD-specific methylation differences were mainly attributed to the APOE ε3/ε4 heterozygous subjects [40]. Allele variations in the major APOE CpG islands of targeted replacement (TR) mice expressing human APOE may affect its methylation in the brain [41]. Epigenetic changes may link modified gene expression with environmental stimuli such as dietary patterns and physical exercise.…”

Section: Apolipoprotein E Human Longevity and Alzheimer's Diseasementioning

confidence: 99%

The Impact of Apolipoprotein E (APOE) Epigenetics on Aging and Sporadic Alzheimer’s Disease

Lozupone,

Dibello,

Sardone

et al. 2023

Biology

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Sporadic Alzheimer’s disease (AD) derives from an interplay among environmental factors and genetic variants, while epigenetic modifications have been expected to affect the onset and progression of its complex etiopathology. Carriers of one copy of the apolipoprotein E gene (APOE) ε4 allele have a 4-fold increased AD risk, while APOE ε4/ε4-carriers have a 12-fold increased risk of developing AD in comparison with the APOE ε3-carriers. The main longevity factor is the homozygous APOE ε3/ε3 genotype. In the present narrative review article, we summarized and described the role of APOE epigenetics in aging and AD pathophysiology. It is not fully understood how APOE variants may increase or decrease AD risk, but this gene may affect tau- and amyloid-mediated neurodegeneration directly or indirectly, also by affecting lipid metabolism and inflammation. For sporadic AD, epigenetic regulatory mechanisms may control and influence APOE expression in response to external insults. Diet, a major environmental factor, has been significantly associated with physical exercise, cognitive function, and the methylation level of several cytosine-phosphate-guanine (CpG) dinucleotide sites of APOE.

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Section: Apolipoprotein E Human Longevity and Alzheimer's Diseasementioning

confidence: 99%