Apolipoprotein E and Alzheimer disease
Strittmatter WJ, Roses AD.. Proceedings of the National Academy of Sciences of the United States of America, 1995-05-01
Topic: Amyloid, tau and blood-test diagnosis
Inheritance of specific apolipoprotein E (apoE) alleles determines, in large part, the risk and mean age of onset of late-onset familial and sporadic Alzheimer disease. The mechanism by which the apoE isoforms differentially contribute to disease expression is, however, unknown. Isoform-specific differences have been identified in the binding of apoE to the microtubule-associated protein tau, which forms the paired helical filament and neurofibrillary tangles, and to amyloid beta peptide, a major component of the neuritic plaque. These and other isoform-specific interactions of apoE give rise to testable hypotheses for the mechanism(s) of pathogenesis of Alzheimer disease. An unresolved issue of increasing importance is the relationship between the structural pathological lesions and the cellular pathogenesis responsible for the clinical disease phenotype, progressive dementia. The identification of apoE in the cytoplasm of human neurons and the characterization of isoform-specific binding of apoE to the microtubule-associated proteins tau and MAP-2 present the possibility that apoE may affect microtubule function in the Alzheimer brain.
Key findings
- The mechanism by which the apoE isoforms differentially contribute to disease expression is, however, unknown.
- Isoform-specific differences have been identified in the binding of apoE to the microtubule-associated protein tau, which forms the paired helical filament and neurofibrillary tangles, and to amyloid beta peptide, a major component of the neuritic plaque.
- These and other isoform-specific interactions of apoE give rise to testable hypotheses for the mechanism(s) of pathogenesis of Alzheimer disease.
- An unresolved issue of increasing importance is the relationship between the structural pathological lesions and the cellular pathogenesis responsible for the clinical disease phenotype, progressive dementia.
- The identification of apoE in the cytoplasm of human neurons and the characterization of isoform-specific binding of apoE to the microtubule-associated proteins tau and MAP-2 present the possibility that apoE may affect microtubule function in the Alzheimer brain.
Why it matters
This review explains that inheriting specific apolipoprotein E alleles largely determines the risk and mean age of onset of late-onset Alzheimer disease, but the mechanism by which the apoE isoforms differentially contribute to disease expression is unknown. It describes isoform-specific interactions of apoE with tau and amyloid beta that give rise to testable hypotheses, but no treatment, cure, or prevention is established.
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Study details
- Evidence strengthLow
How this study scored 50/100
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 | 1995 — 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 700 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 21.2 citations a year over 33 year(s) since 1995 |
| Impact for its field and year | 5 / 6 | Cited 24.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 17 other studies in this library |
| Still being cited | 2 / 4 | Cited 22 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Allen D. Roses: h-index 21 (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 7761390) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 50 / 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).
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APA 7th
Strittmatter, W. J., & Roses, A. D. (1995). Apolipoprotein E and Alzheimer disease. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.92.11.4725
Vancouver
Strittmatter WJ, Roses AD. Apolipoprotein E and Alzheimer disease. Proceedings of the National Academy of Sciences of the United States of America. 1995. doi:10.1073/pnas.92.11.4725. PMID: 7761390.
BibTeX
@article{strittmatter1995-7761390,
author = {Strittmatter, W. J. and Roses, A. D.},
title = {{Apolipoprotein E and Alzheimer disease}},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {1995},
doi = {10.1073/pnas.92.11.4725},
pmid = {7761390},
url = {https://doi.org/10.1073/pnas.92.11.4725}
}
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