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Sex-dependent effect of APOE on Alzheimer's disease and other age-related neurodegenerative disorders.

Publication ,  Journal Article
Gamache, J; Yun, Y; Chiba-Falek, O
Published in: Dis Model Mech
August 27, 2020

The importance of apolipoprotein E (APOE) in late-onset Alzheimer's disease (LOAD) has been firmly established, but the mechanisms through which it exerts its pathogenic effects remain elusive. In addition, the sex-dependent effects of APOE on LOAD risk and endophenotypes have yet to be explained. In this Review, we revisit the different aspects of APOE involvement in neurodegeneration and neurological diseases, with particular attention to sex differences in the contribution of APOE to LOAD susceptibility. We discuss the role of APOE in a broader range of age-related neurodegenerative diseases, and summarize the biological factors linking APOE to sex hormones, drawing on supportive findings from rodent models to identify major mechanistic themes underlying the exacerbation of LOAD-associated neurodegeneration and pathology in the female brain. Additionally, we list sex-by-genotype interactions identified across neurodegenerative diseases, proposing APOE variants as a shared etiology for sex differences in the manifestation of these diseases. Finally, we present recent advancements in 'omics' technologies, which provide a new platform for more in-depth investigations of how dysregulation of this gene affects the development and progression of neurodegenerative diseases. Collectively, the evidence summarized in this Review highlights the interplay between APOE and sex as a key factor in the etiology of LOAD and other age-related neurodegenerative diseases. We emphasize the importance of careful examination of sex as a contributing factor in studying the underpinning genetics of neurodegenerative diseases in general, but particularly for LOAD.

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Published In

Dis Model Mech

DOI

EISSN

1754-8411

Publication Date

August 27, 2020

Volume

13

Issue

8

Location

England

Related Subject Headings

  • Sex Factors
  • Sex Characteristics
  • Risk Factors
  • Risk Assessment
  • Prognosis
  • Phenotype
  • Neurodegenerative Diseases
  • Nerve Degeneration
  • Male
  • Humans
 

Citation

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Gamache, J., Yun, Y., & Chiba-Falek, O. (2020). Sex-dependent effect of APOE on Alzheimer's disease and other age-related neurodegenerative disorders. Dis Model Mech, 13(8). https://doi.org/10.1242/dmm.045211
Gamache, Julia, Young Yun, and Ornit Chiba-Falek. “Sex-dependent effect of APOE on Alzheimer's disease and other age-related neurodegenerative disorders.Dis Model Mech 13, no. 8 (August 27, 2020). https://doi.org/10.1242/dmm.045211.
Gamache J, Yun Y, Chiba-Falek O. Sex-dependent effect of APOE on Alzheimer's disease and other age-related neurodegenerative disorders. Dis Model Mech. 2020 Aug 27;13(8).
Gamache, Julia, et al. “Sex-dependent effect of APOE on Alzheimer's disease and other age-related neurodegenerative disorders.Dis Model Mech, vol. 13, no. 8, Aug. 2020. Pubmed, doi:10.1242/dmm.045211.
Gamache J, Yun Y, Chiba-Falek O. Sex-dependent effect of APOE on Alzheimer's disease and other age-related neurodegenerative disorders. Dis Model Mech. 2020 Aug 27;13(8).
Journal cover image

Published In

Dis Model Mech

DOI

EISSN

1754-8411

Publication Date

August 27, 2020

Volume

13

Issue

8

Location

England

Related Subject Headings

  • Sex Factors
  • Sex Characteristics
  • Risk Factors
  • Risk Assessment
  • Prognosis
  • Phenotype
  • Neurodegenerative Diseases
  • Nerve Degeneration
  • Male
  • Humans