Apolipoprotein epsilon 7 allele in memory complaints: insights through protein structure prediction
- Authors
- Youn, Young Chul; Lim, Yong Kwan; Han, Su-Hyun; Giau, Vo Van; Lee, Mi-Kyung; Park, Kwang-Yeol; Kim, Sang Yun; Bagyinszky, Eva; An, Seong Soo A; Kim, Hye Ryoun
- Issue Date
- Jul-2017
- Publisher
- DOVE MEDICAL PRESS LTD
- Keywords
- apolipoprotein structure; Alzheimer's disease; vascular cognitive impairment; small vessel disease
- Citation
- CLINICAL INTERVENTIONS IN AGING, v.12, pp 1095 - 1102
- Pages
- 8
- Journal Title
- CLINICAL INTERVENTIONS IN AGING
- Volume
- 12
- Start Page
- 1095
- End Page
- 1102
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/6255
- DOI
- 10.2147/CIA.S131172
- ISSN
- 1178-1998
1178-1998
- Abstract
- Purpose: APOE epsilon 7 gene is a rare mutant form of APOE epsilon 3. The mutation occurs in the lipid-binding domain of APOE. Based on the protein's structure, APOE epsilon 7 is expected to function in lipid and beta-amyloid metabolism, similar to APOE epsilon 4. However, unlike that for APOE kappa 4, the mechanisms responsible for Alzheimer's disease (AD) cases associated with APOE epsilon 7 expression have not been elucidated. The present study aims to investigate the association between APOE epsilon 7 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 epsilon 3/epsilon 7 heterozygote individuals who were all classified under the memorycomplaint 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 epsilon 4. APOE K244 or K245 mutations for APOE e7 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 epsilon 7 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 epsilon 7.
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