Cited by 159Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Understanding the association of apolipoprotein E4 with Alzheimer disease: clues from its structure

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Zhong, Ning, Weisgraber, Karl H.·2009·Journal of Biological Chemistry

Abstract

Despite intense interest, the molecular mechanisms underlying the association of apoE4 with Alzheimer disease are not clear. Because the function (or dysfunction) of a protein is based on its structure, this review focuses on the effects of the structural differences among the isoforms on neurodegeneration. Understanding how apoE4 structure impacts neurodegeneration is likely to provide mechanistic insight as well as potential therapeutic approaches to blunt or reduce its effects.

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Crossref · 10.1074/jbc.r800009200

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  • ApoE has two structural domains: an N-terminal domain responsible for interaction with ApoE receptors, and a C-terminal domain responsible for lipoprotein binding.

    “ApoE has two structural domains, an N-terminal domain, which is responsible for interaction with ApoE receptors, and a C-terminal domain, which is responsible for lipoprotein binding [68].”

    From ApoE, ApoE Receptors, and the Synapse in Alzheimer's Disease (2017) · cites this paper as [68]

  • ApoE exists in three isoforms that differ at residues 112 and 158: ApoE2 has cysteine at both positions, ApoE3 has cysteine at position 112 and arginine at position 158, and ApoE4 has arginines at both positions.

    “ApoE exists in the human population in three isoforms, which differ at only two residues, 112 and 158. ApoE2 has a cysteine at both positions, ApoE3 has a cysteine at position 112 and an arginine at position 158, and ApoE4 has arginines at both positions [68].”

    From ApoE, ApoE Receptors, and the Synapse in Alzheimer's Disease (2017) · cites this paper as [68]

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Research works printed but not linked: 9

  1. Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., and Pericak-Vance, M. A. (1993) Science 261, 921-923
  2. Saunders, A. M., Strittmatter, W. J., Schmechel, D., St George-Hyslop, P. H., Pericak-Vance, M. A., Joo, S. H., Rosi, B. L., Gusella, J. F., Crapper- MacLachlan, D. R., Alberts, M. J., Hulette, C., Crain, B., Goldgaber, D., and Roses, A. D. (1993) Neurology 43, 1467-1472
  3. Mahley, R. W., Weisgraber, K. H., and Huang, Y. (2006) Proc. Natl. Acad. Sci. U. S. A. 103, 5644 -5651
  4. Sanan, D. A., Weisgraber, K. H., Russell, S. J., Mahley, R. W., Huang, D., Saunders, A., Schmechel, D., Wisniewski, T., Frangione, B., Roses, A. D., and Strittmatter, W. J. (1994) J. Clin. Investig. 94, 860 -869
  5. Schmechel, D. E., Saunders, A. M., Strittmatter, W. J., Crain, B. J., Hulette, C. M., Joo, S. H., Pericak-Vance, M. A., Goldgaber, D., and Roses, A. D. (1993) Proc. Natl. Acad. Sci. U. S. A. 90, 9649 -9653
  6. Holtzman, D. M., Bales, K. R., Tenkova, T., Fagan, A. M., Parsadanian, M., Sartorius, L. J., Mackey, B., Olney, J., McKeel, D., Wozniak, D., and Paul, S. M. (2000) Proc. Natl. Acad. Sci. U. S. A. 97, 2892-2897
  7. Harris, F. M., Brecht, W. J., Xu, Q., Tesseur, I., Kekonius, L., Wyss-Coray, T., Fish, J. D., Masliah, E., Hopkins, P. C., Scearce-Levie, K., Weisgraber, K. H., Mucke, L., Mahley, R. W., and Huang, Y. (2003) Proc. Natl. Acad. Sci.
  8. Raffaï, R. L., Dong, L.-M., Farese, R. V., Jr., and Weisgraber, K. H. (2001) Proc. Natl. Acad. Sci. U. S. A. 98, 11587-11591
  9. Ye, S., Huang, Y., Mu ¨llendorff, K., Dong, L., Giedt, G., Meng, E. C., Cohen, F. E., Kuntz, I. D., Weisgraber, K. H., and Mahley, R. W. (2005) Proc. Natl. Acad. Sci. U. S. A. 102, 18700 -18705

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Authors
Zhong, N., & Weisgraber, K. H.
Affiliations
Gladstone Institutes (US)
Corresponding author
Weisgraber, Karl H.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2009-03
Volume
284
Issue
10
Pages
6027-6031
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2007282102
Cited by
159
References
43
Citations by year
2026: 6 · 2025: 8 · 2024: 7 · 2023: 7 · 2022: 5 · 2021: 8 · 2020: 13 · 2019: 14 · 2018: 4 · 2017: 6 · 2016: 9 · 2015: 4 · 2014: 12 · 2013: 8 · 2012: 11
FWCI
1.34
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Alzheimer's Association
  • American Health Assistance Foundation
  • Gladstone Institutes
  • National Institutes of Health (CO6 RR0118928, AG‐022074)
  • National Institute on Aging (P01AG022074)
  • National Center for Research Resources (C06 RR0118928)
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 › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
APOE ε4, Alzheimer's disease, APOE isoforms, protein structure, neurodegeneration, molecular mechanisms, therapeutic target
MeSH terms
Alzheimer Disease, Animals, Humans, Structure-Activity Relationship, Protein Structure, Tertiary, Protein Isoforms, Apolipoprotein E4

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