Noncanonical regulation of imprinted gene Igf2 by amyloid-beta 1-42 in Alzheimer's disease.

ABSTRACT: Reduced insulin-like growth factor 2 (IGF2) levels in Alzheimer's disease (AD) may be the mechanism relating age-related metabolic disorders to dementia. Since Igf2 is an imprinted gene, we examined age and sex differences in the relationship between amyloid-beta 1-42 (Aβ₄₂) accumulation and epigenetic regulation of the Igf2/H19 gene cluster in cerebrum, liver, and plasma of young and old male and female 5xFAD mice, in frontal cortex of male and female AD and non-AD patients, and in HEK293 cell cultures. We show IGF2 levels, Igf2 expression, histone acetylation, and H19 ICR methylation are lower in females than males. However, elevated Aβ₄₂ levels are associated with Aβ₄₂ binding to Igf2 DMR2, increased DNA and histone methylation, and a reduction in Igf2 e

SUBMITTER: Fertan E 

PROVIDER: S-EPMC9899226 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature