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Cited by 14Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchLipoproteins and Cardiovascular Health

Apolipoprotein ε7 allele in memory complaints: insights through protein structure prediction

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Youn, Young Chul, Lim, Yong Kwan, Han, Su-Hyun, Giau, Vo Van, Lee, Mi-kyoung, Park, Kwang-Yeol, Kim, SangYun, Bagyinszky, Eva +2 more·2017·Clinical Interventions in Aging
DOI 10.2147/cia.s131172PMC PMC5513808
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Abstract

Purpose: APOE ε7 gene is a rare mutant form of APOE ε3 . The mutation occurs in the lipid-binding domain of APOE. Based on the protein’s structure, APOE ε7 is expected to function in lipid and β-amyloid metabolism, similar to APOE ε4 . However, unlike that for APOE ε4 , the mechanisms responsible for Alzheimer’s disease (AD) cases associated with APOE ε7 expression have not been elucidated. The present study aims to investigate the association between APOE ε7 expression and cognitive impairment. Methods: APOE was sequenced in DNA samples collected from 344 memory-complaint patients who visited the memory clinic, and from 345 non-memory-complaint individuals from the health promotion center. The protein structures of ApoE3, ApoE4, and ApoE7 were predicted. Results: Three ε3/ε7 heterozygote individuals who were all classified under the memory-complaint group were identified. Of these, two subjects were clinically diagnosed with AD with small vessel disease, and the remaining individual was diagnosed with subjective cognitive impairment. This study predicted the protein structures of ApoE3, ApoE4, and ApoE7 and determined the three-dimensional structure of the carboxy terminus of ApoE7, which participates in an electrostatic domain interaction similar to that of APOE ε4 . APOE K244 or K245 mutations for APOE ε7 were not found in the Korean reference genome database, which contains information (http://152.99.75.168/KRGDB/browser/mainBrowser.jsp) from 622 healthy individuals. Conclusion: As verified by the results of structural prediction, APOE ε7 could serve as another risk factor for cognitive impairment and is particularly associated with vascular disease. However, additional studies are required to validate the pathogenic nature of APOE ε7 . Keywords: apolipoprotein structure, Alzheimer’s disease, vascular cognitive impairment, small vessel disease

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  • One case-control study found a higher frequency of a combined Glu262Lys and Glu263Lys variant in patients with memory complaints (P = .08).

    “Furthermore, two case‐studies of patients with frameshift mutations and premature stop codons in exon 4 did not observe clear neurocognitive defects, and one case‐control study found a higher frequency of a combined Glu262Lys and Glu263Lys variant in patients with memory complaints (P = .08) 39 , 40 , 41”

    From <i>APOE</i> and dementia – resequencing and genotyping in 105,597 individuals (2020) · cites this paper as [39]

    The Results (APOE genotype frequencies; page unavailable) report that all three APOE ε7 carriers were in the memory-complaint group and none were in the control group, supporting the higher-frequency comparison. The paper describes the paired substitutions as Glu244Lys and Glu245Lys, not Glu262Lys and Glu263Lys; no passage found reports P = .08 for this comparison. (LLM, conf=0.82)

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  • Two case-studies of patients with frameshift mutations and premature stop codons in exon 4 did not observe clear neurocognitive defects.

    “Furthermore, two case‐studies of patients with frameshift mutations and premature stop codons in exon 4 did not observe clear neurocognitive defects, and one case‐control study found a higher frequency of a combined Glu262Lys and Glu263Lys variant in patients with memory complaints (P = .08) 39 , 40 , 41”

    From <i>APOE</i> and dementia – resequencing and genotyping in 105,597 individuals (2020) · cites this paper as [39]

    The Results (APOE genotype frequencies; page unavailable) describe three carriers of an APOE ε7 variant, including two with cognitive impairment and one with subjective memory complaints. Our copy does not report the two case studies involving frameshift mutations and premature stop codons in exon 4. Searches for those terms found no passage addressing the claimed cases. (LLM, conf=0.75)

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Authors
Youn, Y. C., Lim, Y. K., Han, S.-H., Giau, V. V., Lee, M.-K., Park, K.-Y., Kim, S., Bagyinszky, E., An, S. S., & Kim, H. R.
Affiliations
  • Chung-Ang University (KR)
  • Gachon University (KR)
  • Seoul National University (KR)
Corresponding author
  • An, Seong Soo
  • Kim, Hye Ryoun
ORCID
Venue
Clinical Interventions in Aging
Publisher
Informa UK Limited
Published
2017-07
Volume
Volume 12
Pages
1095-1102
ISSN
  • 1176-9092 (ISSN-L)
  • 1178-1998
DOI
10.2147/cia.s131172
PMC
PMC5513808
OpenAlex
W2735129431
Cited by
14
References
2
Citations by year
2025: 2 · 2024: 2 · 2023: 1 · 2022: 2 · 2020: 1 · 2019: 5 · 2018: 1
FWCI
1.36
Type
journal article
Language
en
Open access
Licence
Locations
  • Clinical Interventions in Aging (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Dove Medical Press (Taylor and Francis Group) (acceptedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Research Foundation
  • Chung-Ang University
  • Korea Health Industry Development Institute (HI14C3331)
  • National Research Foundation of Korea (NRF-2017R1A2B4011631)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Keywords
Alzheimer's disease, vascular cognitive impairment, cerebral small vessel disease, memory impairment, subjective cognitive impairment, protein structure prediction, lipid-binding domain
MeSH terms
Aged, Alleles, Alzheimer Disease, Apolipoproteins E, Female, Humans, Male, Memory, Middle Aged, Problem Solving, Risk Factors, Apolipoprotein E3, Apolipoprotein E4, Republic of Korea, Cognitive Dysfunction

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