Cited by 183Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

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The forgotten APOE allele: A review of the evidence and suggested mechanisms for the protective effect of APOE ɛ2

Suri, Sana, Heise, Verena, Trachtenberg, Aaron J., Mackay, Clare E.·2013·Neuroscience & Biobehavioral Reviews

DOI 10.1016/j.neubiorev.2013.10.010

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Abstract

Ongoing efforts to improve survival, and enhance quality of life have led biomedical research to focus on disease and the mechanisms that increase risk for disease. The other side of that coin may be as important, i.e. examining the protective factors that allow some individuals to enjoy long, healthy lives. One of the best examples of a gene that positively influences cognitive health is the apolipoprotein (APOE) ɛ2 allele. The APOE ɛ4 allele is a well-established risk factor for Alzheimer's disease (AD) and has thus dominated the APOE literature, with the putative protective role of ɛ2 receiving little attention. This review describes the effects of APOE ɛ2 on the structure and function of the brain. With a focus on neurodegeneration, we discuss evidence for APOE ɛ2's protective effects, explore some key mechanisms through which this protection may be conferred, and address a few inconsistencies in the literature. Understanding the mechanisms that underlie the association between APOE ɛ2, cognition and longevity may provide new targets for research on promoting life-long health.

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Authors: Suri, S., Heise, V., Trachtenberg, A. J., & Mackay, C. E.
Affiliations: John Radcliffe Hospital (GB)
Corresponding author: Mackay, Clare E.
ORCID: Suri, Sana
Heise, Verena
Trachtenberg, Aaron J.
Mackay, Clare E.
Venue: Neuroscience & Biobehavioral Reviews
Publisher: Elsevier BV
Published: 2013-12
Volume: 37
Issue: 10
Pages: 2878-2886
ISSN: 0149-7634 (ISSN-L)
DOI: 10.1016/j.neubiorev.2013.10.010
OpenAlex: W2067079625
Cited by: 183
References: 126
Citations by year: 2026: 6 · 2025: 9 · 2024: 14 · 2023: 15 · 2022: 15 · 2021: 24 · 2020: 26 · 2019: 14 · 2018: 11 · 2017: 14 · 2016: 18 · 2015: 14 · 2014: 3
FWCI: 1.29
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neuroscience & Biobehavioral Reviews (publishedVersion)
PubMed (publishedVersion)
Funders: University of Oxford Clarendon scholarship
Alzheimer's Research UK studentship
Rhodes scholarship
National Institute for Health Research (NIHR), UK
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: APOE ε2 allele, APOE ε4, apolipoprotein E, Alzheimer's disease, neuroprotection, cognitive health, longevity, neurodegeneration, brain structure and function, protective genetic factor
MeSH terms: Alleles, Cognition Disorders, Genotype, Humans, Longevity, Risk Factors, Neurodegenerative Diseases, Apolipoprotein E2

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The forgotten APOE allele: A review of the evidence and suggested mechanisms for the protective effect of APOE ɛ2

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