Topic: Brain proteins, microglia and lab models
The epsilon 4 allele of apolipoprotein E (APOE) has been found to be a risk factor for late-onset Alzheimer's disease (AD). While the pathogenic mechanism of APOE in AD is not yet clear, APOE isoforms appear to differentially influence the aggregation of A beta, the principal component of Alzheimer-associated beta-amyloid deposits. To date, no data are available for the propensity of A beta to aggregate in the presence of APOE under conditions where these components are at physiological concentrations (in cerebrospinal fluid, APOE and A beta are approximately 100 nM and approximately 5 nM, respectively). We employed a novel in vitro filtration assay for detecting zinc(II)- and copper(II)-induced aggregation of A beta in solutions containing concentrations of the peptide that are similar to those reported for human cerebrospinal fluid. The potential for resolubilization with EDTA and the relative densities of zinc- and copper-induced A beta aggregates were also compared. Zinc-induced A beta aggregates were found to be denser and less easily resolubilized than copper-induced precipitates. Metal-induced aggregation of A beta was studied in the presence of purified apolipoprotein E2, apolipoprotein E3, and apolipoprotein E4 under conditions that approximate the physiological concentrations and ratios of these proteins. In the presence of all three APOE isoforms, zinc-induced aggregation of A beta was attenuated, while precipitation with copper was enhanced. Consistent with the increased risk for AD associated with the epsilon 4 allele of APOE, metal-induced aggregation of A beta was highest for both zinc and copper in the presence of apolipoprotein E4. Our data are consistent with a role for APOE as an in vivo molecular chaperone for A beta.
Key findings
- Consistent with the increased risk for AD associated with the epsilon 4 allele of APOE, metal-induced aggregation of A beta was highest for both zinc and copper in the presence of apolipoprotein E4.
Why it matters
In laboratory experiments, zinc- and copper-induced clumping of beta-amyloid was highest when apolipoprotein E4 was present, matching the higher Alzheimer risk linked to the epsilon 4 allele. This is in-vitro work only and does not show that preventing this clumping treats or prevents Alzheimer disease in people.
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Study details
- Evidence strengthLow
How this study scored 44/100
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 (Biochemistry) |
| Journal's citation record | 3 / 4 | Biochemistry: journal h-index 442 (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 | 1999 — 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 | 5 / 7 | Cited 110 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 3.8 citations a year over 29 year(s) since 1999 |
| Impact for its field and year | 3 / 6 | Cited 4.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 4 other studies in this library |
| Still being cited | 1 / 4 | Cited 4 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Rudolph E. Tanzi: h-index 145 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Massachusetts General Hospital: institution h-index 2,057 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 10194381) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 44 / 100 | — |
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Read the original
May need a subscription Unpaywall, Europe PMC and OpenAlex found no free copy of the full text (checked 10 Oct 2026), so the publisher may charge for it. The PubMed abstract is free.
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 8 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
Moir, R. D., Atwood, C. S., Romano, D. M., Laurans, M. H., Huang, X., Bush, A. I., et al. (1999). Differential effects of apolipoprotein E isoforms on metal-induced aggregation of A beta using physiological concentrations. Biochemistry. https://doi.org/10.1021/bi982437d
Vancouver
Moir RD, Atwood CS, Romano DM, Laurans MH, Huang X, Bush AI, et al. Differential effects of apolipoprotein E isoforms on metal-induced aggregation of A beta using physiological concentrations. Biochemistry. 1999. doi:10.1021/bi982437d. PMID: 10194381.
BibTeX
@article{moir1999-10194381,
author = {Moir, R. D. and Atwood, C. S. and Romano, D. M. and Laurans, M. H. and Huang, X. and Bush, A. I. and Smith, J. D. and Tanzi, R. E.},
title = {{Differential effects of apolipoprotein E isoforms on metal-induced aggregation of A beta using physiological concentrations}},
journal = {Biochemistry},
year = {1999},
doi = {10.1021/bi982437d},
pmid = {10194381},
url = {https://doi.org/10.1021/bi982437d}
}
Later studies that cite this one
4 studies in the alzhub library list this one in their references.