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APOE alleles and diet in brain aging and Alzheimer's disease

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Yassine, Hussein N., Finch, Caleb E.·2020·Frontiers in Aging Neuroscience
DOI 10.3389/fnagi.2020.00150PMC PMC7297981
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Abstract

The APOE gene alleles modify human aging and the response to the diet at many levels with diverse pleotropic effects from gut to brain. To understand interactions of APOE isoforms and diet, we analyze how cellular trafficking of apoE proteins affects energy metabolism, the immune system and reproduction. The age-accelerating APOE4 allele alters endosomal trafficking of cell surface receptors that mediate lipid and glucose metabolism. The APOE4 allele is the ancestral human allele, joined by APOE3 and then APOE2 in the human species. Under conditions of high infection, uncertain food, and shorter life expectancy, APOE4 may be adaptive for reducing mortality. As humans transitioned into modern less-infectious environments and longer life spans, APOE4 increased risks of aging-related diseases, particularly impacting arteries and brain. The association of APOE4 with glucose dysregulation and body weight promotes many aging-associated diseases. Additionally, the APOE gene locus interacts with adjacent genes on chromosome 19 in haplotypes that modify neurodegeneration and metabolism, for which we anticipate complex gene environment interactions. We summarize how diet and AD risk are altered by APOE genotype in both animal and human studies and identify gaps. Much remains obscure in how APOE alleles modify nutritional factors in human aging. Identifying risk variant haplotypes in the APOE gene complex will clarify homeostatic adaptive responses to environmental conditions.

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  • APOE4 interacts with insulin receptors and other transporters, relocating them to the endosomal compartment; a similar mechanism may affect EAAT and GLAST surface expression, ultimately decreasing glutamate uptake capacity in APOE4 iAstrocytes.

    “APOE4 also interacts with insulin receptors and other transporters, relocating them to the endosomal compartment: a similar mechanism may also affect excitatory amino acid transporter (EAAT) and glutamate/aspartate transporter (GLAST) surface expression, ultimately decreasing glutamate uptake capacity in the APOE4 iAstrocytes (Yassine and Finch, 2020).”

    From APOE2, E3, and E4 differentially modulate cellular homeostasis, cholesterol metabolism, and inflammatory response in isogenic iPSC-derived astrocytes (2022) · cites this paper as Yassine and Finch, 2020

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Cited by

Sorted by citations

Authors
Yassine, H. N., & Finch, C. E.
Affiliations
University of Southern California (US)
Corresponding author
Yassine, Hussein N.
ORCID
Venue
Frontiers in Aging Neuroscience
Publisher
Frontiers Media SA
Published
2020-06-10
Volume
12
Pages
150-150
ISSN
1663-4365 (ISSN-L)
DOI
10.3389/fnagi.2020.00150
PMC
PMC7297981
OpenAlex
W3035581459
Cited by
145
References
20
Citations by year
2026: 25 · 2025: 22 · 2024: 18 · 2023: 26 · 2022: 25 · 2021: 27 · 2020: 1
FWCI
2.51
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Aging Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Institute on Aging
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
APOE alleles, APOE ε4, Alzheimer's disease, brain aging, diet, endosomal trafficking, energy metabolism, glucose metabolism, immune system, reproduction, APOE haplotypes, gene-environment interaction, adaptive evolution, neurodegeneration, chromosome 19

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