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

Madia Lozupone; Vittorio Dibello; Rodolfo Sardone; Fabio Castellana; Roberta Zupo; Luisa Lampignano; Ilaria Bortone; Antonio Daniele; Antonello Bellomo; Vincenzo Solfrizzi; Francesco Panza

doi:10.20944/preprints202311.0227.v1

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preprints.org > biology and life sciences > aging > doi: 10.20944/preprints202311.0227.v1

Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

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

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Version 1 : Received: 2 November 2023 / Approved: 3 November 2023 / Online: 3 November 2023 (10:00:30 CET)

A peer-reviewed article of this Preprint also exists.

Lozupone, M.; Dibello, V.; Sardone, R.; Castellana, F.; Zupo, R.; Lampignano, L.; Bortone, I.; Daniele, A.; Bellomo, A.; Solfrizzi, V.; Panza, F. The Impact of Apolipoprotein E (APOE) Epigenetics on Aging and Sporadic Alzheimer’s Disease. Biology 2023, 12, 1529. Lozupone, M.; Dibello, V.; Sardone, R.; Castellana, F.; Zupo, R.; Lampignano, L.; Bortone, I.; Daniele, A.; Bellomo, A.; Solfrizzi, V.; Panza, F. The Impact of Apolipoprotein E (APOE) Epigenetics on Aging and Sporadic Alzheimer’s Disease. Biology 2023, 12, 1529.

Abstract

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. Heterozygous carriers of the apolipoprotein E gene (APOE)4 allele have a 4-fold increased risk of developing AD, while APOE 4/4-carriers have a 12-fold increased risk in comparison with the APOE 3-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 is known to affect amyloid- and tau-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 significant associated with physical exercise, cognitive function, and the methylation level of several cytosine-phosphate-guanine (CpG) dinucleotides sites of APOE.

Keywords

apolipoprotein E; Alzheimer’s disease; methylation; dementia; epigenetics; tau protein; amyloid-β; longevity

Subject

Biology and Life Sciences, Aging

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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