Isoform-specific interactions of apolipoprotein E with microtubule-associated protein tau: implications for Alzheimer disease.
Open accessAbstract
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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Cholinergic systems and long-term potentiation in memory-impaired apolipoprotein E-deficient mice
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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
- Publisher
- National Academy of Sciences
- Published
- 1994-11-08
- Volume
- 91
- Issue
- 23
- Pages
- 11183-11186
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC45191
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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