Isoform-specific interactions of apolipoprotein E with microtubule-associated protein tau: implications for Alzheimer disease
Strittmatter WJ, Saunders AM, Goedert M, Weisgraber KH, Dong LM, Jakes R, Huang DY, Pericak-Vance M et al.. Proceedings of the National Academy of Sciences of the United States of America, 1994-11-01
Topic: Amyloid, tau and blood-test diagnosis
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.
Key findings
- 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.
Why it matters
In this in vitro study, tau bound avidly to apoE3 but not to apoE4, and tau phosphorylated with a brain extract did not bind either isoform. The authors suggest that isoform-specific interactions of apoE with tau may regulate intraneuronal tau metabolism and alter the rate of formation of paired helical filaments and neurofibrillary tangles, but this is laboratory work with no demonstrated treatment, cure, or prevention.
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Study details
- Evidence strengthLow
How this study scored 49/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Proceedings of the National Academy of Sciences of the United States of America) |
| Journal's citation record | 4 / 4 | Proceedings of the National Academy of Sciences: journal h-index 1,167 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 1994 — older than 20 years, still counted |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 476 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 14.0 citations a year over 34 year(s) since 1994 |
| Impact for its field and year | 4 / 6 | Cited 17.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 21 other studies in this library |
| Still being cited | 2 / 4 | Cited 28 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Allen D. Roses: h-index 94 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Duke University: institution h-index 1,541 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 7972031) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 49 / 100 | — |
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Read the original
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Strittmatter, W. J., Saunders, A. M., Goedert, M., Weisgraber, K. H., Dong, L. M., Jakes, R., et al. (1994). Isoform-specific interactions of apolipoprotein E with microtubule-associated protein tau: implications for Alzheimer disease. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.91.23.11183
Vancouver
Strittmatter WJ, Saunders AM, Goedert M, Weisgraber KH, Dong LM, Jakes R, et al. Isoform-specific interactions of apolipoprotein E with microtubule-associated protein tau: implications for Alzheimer disease. Proceedings of the National Academy of Sciences of the United States of America. 1994. doi:10.1073/pnas.91.23.11183. PMID: 7972031.
BibTeX
@article{strittmatter1994-7972031,
author = {Strittmatter, W. J. and Saunders, A. M. and Goedert, M. and Weisgraber, K. H. and Dong, L. M. and Jakes, R. and Huang, D. Y. and Pericak-Vance, M. and others},
title = {{Isoform-specific interactions of apolipoprotein E with microtubule-associated protein tau: implications for Alzheimer disease}},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {1994},
doi = {10.1073/pnas.91.23.11183},
pmid = {7972031},
url = {https://doi.org/10.1073/pnas.91.23.11183}
}
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