Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease
David M. Holtzman, Kelly R. Bales, Tanya Tenkova, Anne M. Fagan, Maia Parsadanian, Leah J. Sartorius, Brian Mackey, John W. Olney, Daniel W. McKeel, David F. Wozniak, Steven M. Paul. Proceedings of the National Academy of Sciences, 2000-02-29
Topic: Brain proteins, microglia and lab models
Apolipoprotein E (apoE) alleles determine the age-adjusted relative risk (epsilon4 > epsilon3) for Alzheimer's disease (AD). ApoE may affect AD pathogenesis by promoting deposition of the amyloid-beta (Abeta) peptide and its conversion to a fibrillar form. To determine the effect of apoE on Abeta deposition and AD pathology, we compared APP(V717F) transgenic (TG) mice expressing mouse, human, or no apoE (apoE(-/-)). A severe, plaque-associated neuritic dystrophy developed in APP(V717F) TG mice expressing mouse or human apoE. Though significant levels of Abeta deposition also occurred in APP(V717F) TG, apoE(-/-) mice, neuritic degeneration was virtually absent. Expression of apoE3 and apoE4 in APP(V717F) TG, apoE(-/-) mice resulted in fibrillar Abeta deposits and neuritic plaques by 15 months of age and substantially (>10-fold) more fibrillar deposits were observed in apoE4-expressing APP(V717F) TG mice. Our data demonstrate a critical and isoform-specific role for apoE in neuritic plaque formation, a pathological hallmark of AD.
Why it matters
In amyloid-forming mice, those lacking apoE still built up amyloid but neuritic degeneration was virtually absent, and mice expressing human apoE4 had more than 10-fold more fibrillar deposits. The authors conclude apoE plays a critical, isoform-specific role in neuritic plaque formation.
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How this study scored 52/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it. We have no data on strength of evidence, so that was left out: it earned 49 of the 95 points we could judge it on, which is 52 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Proceedings of the National Academy of Sciences) |
| 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 | — / 5 | No evidence rating recorded — left out of this score |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2000 — 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 | Laboratory or animal study (title names “mouse”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 942 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 33.6 citations a year over 28 year(s) since 2000 |
| Impact for its field and year | 5 / 6 | Cited 29.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 3 / 4 | Cited 87 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Steven M. Paul: h-index 81 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Washington University in St. Louis: institution h-index 1,962 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 10694577) |
| Free to read | 2 / 2 | Free to read |
| Points | 49 / 95 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 49 of the 95 points we could judge it on is 52 out of 100. |
| Total | 52 / 100 | — |
What each of these 20 components measures, and what this score is not →
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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 names 11 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Holtzman, D. M., Bales, K. R., Tenkova, T., Fagan, A. M., Parsadanian, M., Sartorius, L. J., et al. (2000). Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.050004797
Vancouver
Holtzman DM, Bales KR, Tenkova T, Fagan AM, Parsadanian M, Sartorius LJ, et al. Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease. Proceedings of the National Academy of Sciences. 2000. doi:10.1073/pnas.050004797. PMID: 10694577.
BibTeX
@article{holtzman2000-10694577,
author = {Holtzman, David M. and Bales, Kelly R. and Tenkova, Tanya and Fagan, Anne M. and Parsadanian, Maia and Sartorius, Leah J. and Mackey, Brian and Olney, John W. and McKeel, Daniel W. and Wozniak, David F. and Paul, Steven M.},
title = {{Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease}},
journal = {Proceedings of the National Academy of Sciences},
year = {2000},
doi = {10.1073/pnas.050004797},
pmid = {10694577},
url = {https://doi.org/10.1073/pnas.050004797}
}