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Cited by 113Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchGenetic Associations and Epidemiology

The Neurobiology and Age-Related Prevalence of the ε4 Allele of Apolipoprotein E in Alzheimer’s Disease Cohorts

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Heffernan, Amy L., Chidgey, Cameron, Peng, Po, Masters, Colin L., Roberts, Blaine R.·2016·Journal of Molecular Neuroscience
DOI 10.1007/s12031-016-0804-xPMC PMC5531868
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Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterised by amyloid beta (Aβ) plaques and tau neurofibrillary tangles in the brain. Human apolipoprotein E (ApoE) is a lipid transport protein coded by the polymorphic APOE gene, with three major alleles: ε2, ε3 and ε4. After age, the ε4 allele is the greatest risk factor for developing sporadic AD, conferring an increased risk of 3-4 and 8-12 times for one or two copies of the allele, respectively. This risk is reported to vary by demographic factors including sex, ethnicity and geography. In order to understand the risk of ApoE ε4 in relation to age, the primary risk factor for developing AD, we need to understand how the prevalence of APOE genotypes changes with age. Here, we present the first data on age-related prevalence of APOE ε4 in AD in three AD cohorts in Australia and the USA. There is a significant association between age and ε4 prevalence, particularly for ε4 homozygotes, such that as age increases the prevalence of ε4 decreases. Further studies on a random, population-based sample of the population are needed to provide more generalizable data, particularly in the >90-year-old age group.

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  • After age, polymorphisms of the APOE gene are the biggest risk factor for the development of Alzheimer's disease.

    “After age, polymorphisms of the Apolipoprotein E (APOE) gene are the biggest risk factor for the development of Alzheimer’s disease (AD).”

    From Discovery of a Missense Mutation (Q222K) of the <i>APOE</i> Gene from the Australian Imaging, Biomarker and Lifestyle Study (2023) · cites this paper as [1]

    The Abstract says that, after age, the APOE ε4 allele is the greatest risk factor for developing sporadic Alzheimer’s disease; the Introduction likewise calls it the major single genetic risk factor for sporadic forms. The citing sentence broadens this from the ε4 allele to APOE polymorphisms generally, and from sporadic disease to Alzheimer’s disease without qualification. (LLM, conf=0.86)

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  • The ε4 homozygous genotype has a relatively low prevalence in clinical populations.

    “which reflects the relatively low prevalence of this genotype in clinical populations [35]”

    From Plasma ApoE proteotyping for ApoE ε4 stratification in the anti-amyloid therapies era (2026) · cites this paper as [35]

  • The relatively small number of ε4 homozygotes in this cohort (n = 9) represents a limitation and may reduce the robustness of subgroup analyses, particularly for genotype stratification.

    “The relatively small number of ε4 homozygotes in our cohort (n = 9), which reflects the relatively low prevalence of this genotype in clinical populations [35], represents a limitation and may reduce the robustness of subgroup analyses, particularly for genotype stratification.”

    From Plasma ApoE proteotyping for ApoE ε4 stratification in the anti-amyloid therapies era (2026) · cites this paper as [35]

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Authors
Heffernan, A. L., Chidgey, C., Peng, P., Masters, C. L., & Roberts, B. R.
Affiliations
The University of Melbourne (AU)
Corresponding author
Roberts, Blaine R.
ORCID
Venue
Journal of Molecular Neuroscience
Publisher
Springer Science and Business Media LLC
Published
2016-08-06
Volume
60
Issue
3
Pages
316-324
ISSN
  • 0895-8696 (ISSN-L)
  • 1559-1166
DOI
10.1007/s12031-016-0804-x
PMC
PMC5531868
OpenAlex
W2491120843
Cited by
113
References
64
Citations by year
2026: 5 · 2025: 10 · 2024: 18 · 2023: 13 · 2022: 17 · 2021: 14 · 2020: 15 · 2019: 14 · 2018: 4 · 2017: 2 · 2016: 1
FWCI
0.82
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (unspecified)
Locations
  • Journal of Molecular Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Health and Medical Research Council (APP1106911)
  • Australian Postgraduate Award
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords
Alzheimer's disease, apolipoprotein E, APOE ε4, age-related prevalence, genetic risk factors, sporadic Alzheimer's disease, amyloid plaques, neurofibrillary tangles
MeSH terms
Age Factors, Alzheimer Disease, Apolipoproteins E, Australia, Brain, Gene Frequency, Humans, Prevalence

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