Cited by 474Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Isoform-specific interactions of apolipoprotein E with microtubule-associated protein tau: implications for Alzheimer disease.

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Strittmatter, W J, Saunders, A M, Goedert, M, Weisgraber, K H, Dong, L M, Jakes, R, Huang, D Y, Pericak-Vance, M +2 more·1994·Proceedings of the National Academy of Sciences

Abstract

The apolipoprotein E (apoE) type 4 allele (APOE4) is a susceptibility gene for late-onset familial and sporadic Alzheimer disease. ApoE is found in some neurofibrillary tangle-bearing neurons, one of the major pathologic hallmarks of the disease. Neurofibrillary tangles contain paired helical filaments formed from hyperphosphorylated microtubule-associated protein tau. In vitro, tau binds avidly to apoE3, but not to apoE4, forming a bimolecular complex. Tau phosphorylated with a brain extract does not bind either isoform. ApoE3 binds to the microtubule-binding repeat region of tau, which is also the region that is thought to cause self-assembly into the paired helical filament. Binding studies with fragments of ApoE demonstrate that the tau-binding region of apoE3 corresponds to its receptor-binding domain and is distinct from the region that binds lipoprotein particles or beta/A4 peptide. Isoform-specific interactions of apoE with tau may regulate intraneuronal tau metabolism in Alzheimer disease and alter the rate of formation of paired helical filaments and neurofibrillary tangles.

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Crossref · 10.1073/pnas.91.23.11183

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Authors
Strittmatter, W. J., Saunders, A. M., Goedert, M., Weisgraber, K. H., Dong, L. M., Jakes, R., Huang, D. Y., Pericak-Vance, M., Schmechel, D., & Roses, A. D.
Affiliations
  • Duke University (US)
  • Department of Medicine (Neurology), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC 27710.
Venue
Proceedings of the National Academy of Sciences
Published
1994-11-08
Volume
91
Issue
23
Pages
11183-11186
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2010390315
Cited by
474
References
41
Citations by year
2026: 7 · 2025: 11 · 2024: 10 · 2023: 4 · 2022: 15 · 2021: 14 · 2020: 9 · 2019: 20 · 2018: 10 · 2017: 11 · 2016: 13 · 2015: 14 · 2014: 13 · 2013: 10 · 2012: 7
FWCI
18.10
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r35ag007922-07)
  • National Institute on Aging (5 R35-AG-07922, P50AG005128, 5P50AG05128)
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
apolipoprotein E, APOE ε4, tau protein, Alzheimer's disease, neurofibrillary tangles, paired helical filaments, tau phosphorylation, receptor binding domain, APOE3
MeSH terms
Alzheimer Disease, Apolipoproteins E, Binding Sites, Humans, Phosphoproteins, Protein Binding, Recombinant Proteins, tau Proteins, In Vitro Techniques

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