Apolipoprotein E affects amyloid formation but not amyloid growth in vitro: mechanistic implications for apoE4 enhanced amyloid burden and risk for Alzheimer's disease
William P Esler, Jeffrey R Marshall, Evelyn R Stimson, Joseph R Ghilardi, Harry V Vinters, Patrick W Mantyh, John E Maggio. Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis, 2002-03
Topic: Genetics and APOE
The transition from the partially folded soluble Abeta monomer to insoluble Abeta amyloidfibrils is seminal to the formation and growth of amyloid plaques in Alzheimer's disease (AD). A detailed understanding of the role of AD risk factors in these processes is essential to understanding the physiochemical nature of this conformational rearrangement. The apolipoprotein E epsilon4 allele, a risk factor for AD, affects AD pathology by increasing amyloid burden relative to the much more common epsilon3 allele. In the present study, in vitro models were employed to probe the effect of these proteins on kinetically distinct steps in Abeta fibrillogenesis. Formation of Abeta amyloid was faster in the presence of apoE4 than apoE3, while growth of existing plaques was unaffected by either isoform. Further, experiments with Abeta stereoisomers establish that this effect of apoE3 is mediated through interaction with oligomeric fibrillogenic intermediates rather than through specific contacts with monomeric Abeta. Consistent with the altered pathology and enhanced risk for AD associated with inheritance of the epsilon4 allele, we conclude that APOE epsilon4 is a risk factor for AD not due to a pathological gain of function of apoE4 but to a loss of protective function of apoE3.
Key findings
- Consistent with the altered pathology and enhanced risk for AD associated with inheritance of the epsilon4 allele, we conclude that APOE epsilon4 is a risk factor for AD not due to a pathological gain of function of apoE4 but to a loss of protective function of apoE3.
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Study details
- Evidence strengthLow
How this study scored 38/100
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 journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 21 of the 56 points we could judge it on, which is 38 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 2002 — 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 “in vitro”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 12000192) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 21 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 21 of the 56 points we could judge it on is 38 out of 100. |
| Total | 38 / 100 | — |
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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 7 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
Esler, W. P., Marshall, J. R., Stimson, E. R., Ghilardi, J. R., Vinters, H. V., Mantyh, P. W., et al. (2002). Apolipoprotein E affects amyloid formation but not amyloid growth in vitro: mechanistic implications for apoE4 enhanced amyloid burden and risk for Alzheimer's disease. Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis. https://doi.org/10.3109/13506120209072439
Vancouver
Esler WP, Marshall JR, Stimson ER, Ghilardi JR, Vinters HV, Mantyh PW, et al. Apolipoprotein E affects amyloid formation but not amyloid growth in vitro: mechanistic implications for apoE4 enhanced amyloid burden and risk for Alzheimer's disease. Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis. 2002. doi:10.3109/13506120209072439. PMID: 12000192.
BibTeX
@article{esler2002-12000192,
author = {Esler, William P and Marshall, Jeffrey R and Stimson, Evelyn R and Ghilardi, Joseph R and Vinters, Harry V and Mantyh, Patrick W and Maggio, John E},
title = {{Apolipoprotein E affects amyloid formation but not amyloid growth in vitro: mechanistic implications for apoE4 enhanced amyloid burden and risk for Alzheimer's disease}},
journal = {Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis},
year = {2002},
doi = {10.3109/13506120209072439},
pmid = {12000192},
url = {https://doi.org/10.3109/13506120209072439}
}
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