The Impact of Apolipoprotein E () Epigenetics on Aging and Sporadic Alzheimer's Disease.

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 () allele have a 4-fold increased AD risk, while -carriers have a 12-fold increased risk of developing AD in comparison with the -carriers. The main longevity factor is the homozygous ε3/ε3 genotype. In the present narrative review article, we summarized and described the role of epigenetics in aging and AD pathophysiology. It is not fully understood how 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 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 .