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Cited by 137Genetics, Aging, and Longevity in Model OrganismsMitochondrial Function and PathologyAlzheimer's disease research and treatments

APOE genotype and stress response - a mini review

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Dose, Janina, Huebbe, Patricia, Nebel, Almut, Rimbach, Gerald·2016·Lipids in Health and Disease
DOI 10.1186/s12944-016-0288-2PMC PMC4960866
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Abstract

The APOE gene is one of currently only two genes that have consistently been associated with longevity. Apolipoprotein E (APOE) is a plasma protein which plays an important role in lipid and lipoprotein metabolism. In humans, there are three major APOE isoforms, designated APOE2, APOE3, and APOE4. Of these three isoforms, APOE3 is most common while APOE4 was shown to be associated with age-related diseases, including cardiovascular and Alzheimer's disease, and therefore an increased mortality risk with advanced age. Evidence accumulates, showing that oxidative stress and, correspondingly, mitochondrial function is affected in an APOE isoform-dependent manner. Accordingly, several stress response pathways implicated in the aging process, including the endoplasmic reticulum stress response and immune function, appear to be influenced by the APOE genotype. The investigation and development of treatment strategies targeting APOE4 have not resolved any therapeutic yet that could be entirely recommended. This mini-review provides an overview on the state of research concerning the impact of the APOE genotype on stress response-related processes, emphasizing the strong interconnection between mitochondrial function, endoplasmic reticulum stress and the immune response. Furthermore, this review addresses potential treatment strategies and associated pitfalls as well as lifestyle interventions that could benefit people with an at risk APOE4 genotype.

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  • Several studies demonstrated a link between APOE4 and mitochondrial dysfunction, mainly in neurons.

    “Several studies demonstrated a link between APOE4 and mitochondrial dysfunction, mainly in neurons9–11; yet the effect of APOE4 on mitochondrial dynamics was less studied.”

    From Altered mitochondrial dynamics and function in APOE4-expressing astrocytes (2020) · cites this paper as [9]

  • In stressful circumstances, APOE ε4 allele carriers are at increased risk of mental illness.

    “in stressful circumstances, APOE ε4 allele carriers are at an increased risk of mental illness [8, 9]”

    From APOE4 genotype exacerbates the depression-like behavior of mice during aging through ATP decline (2021) · cites this paper as [9]

    The Background section links APOE ε4 to increased risk of late-onset Alzheimer’s disease, and the Conclusion discusses its role in cellular stress responses. Neither passage establishes that carriers face increased risk of mental illness in stressful circumstances. Searches for mental illness, psychiatric conditions, and psychosocial stress found no passage addressing that claim. (LLM, conf=0.76)

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Cited by

Sorted by citations

Authors
Dose, J., Huebbe, P., Nebel, A., & Rimbach, G.
Affiliations
Christian-Albrechts-Universität zu Kiel (DE)
Corresponding author
Dose, Janina
ORCID
Venue
Lipids in Health and Disease
Publisher
Springer Science and Business Media LLC
Published
2016-07-25
Volume
15
Issue
1
Pages
121-121
ISSN
1476-511X (ISSN-L)
DOI
10.1186/s12944-016-0288-2
PMC
PMC4960866
OpenAlex
W2487415734
Cited by
137
References
18
Citations by year
2026: 13 · 2025: 9 · 2024: 19 · 2023: 19 · 2022: 12 · 2021: 16 · 2020: 16 · 2019: 12 · 2018: 12 · 2017: 9
FWCI
1.12
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Lipids in Health and Disease (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Deutsche Forschungsgemeinschaft (RTG1743/1)
  • Land Schleswig-Holstein (Open Access Publikationsfonds)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
APOE genotype, APOE ε4, apolipoprotein E isoforms, stress response, aging, longevity, oxidative stress, mitochondrial function, endoplasmic reticulum stress, immune response, age-related diseases, Alzheimer's disease, cardiovascular disease, lifestyle intervention
MeSH terms
Alzheimer Disease, Cardiovascular Diseases, Endoplasmic Reticulum, Genotype, Humans, Immunity, Innate, Liver, Longevity, Mitochondria, Gene Expression, Survival Analysis, Oxidative Stress, Apolipoprotein E3, Apolipoprotein E4, Apolipoprotein E2, Endoplasmic Reticulum Stress

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