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Identification of disulfiram as a secretase-modulating compound with beneficial effects on Alzheimer's disease hallmarks
Reinhardt S, Stoye N, Luderer M, Kiefer F, Schmitt U, Lieb K, Endres K.. Scientific reports, 2018-01-22
Topic: Amyloid, tau and blood-test diagnosis
ADAM10 is a metalloproteinase acting on the amyloid precursor protein (APP) as an alpha-secretase in neurons. Its enzymatic activity results in secretion of a neuroprotective APP cleavage product (sAPP-alpha) and prevents formation of the amyloidogenic A-beta peptides, major hallmarks of Alzheimer's disease (AD). Elevated ADAM10 levels appeared to contribute to attenuation of A-beta-plaque formation and learning and memory deficits in AD mouse models. Therefore, it has been assumed that ADAM10 might represent a valuable target in AD therapy. Here we screened a FDA-approved drug library and identified disulfiram as a novel ADAM10 gene expression enhancer. Disulfiram increased ADAM10 production as well as sAPP-alpha in SH-SY5Y human neuronal cells and additionally prevented A-beta aggregation in an in vitro assay in a dose-dependent fashion. In addition, acute disulfiram treatment of Alzheimer model mice induced ADAM10 expression in peripheral blood cells, reduced plaque-burden in the dentate gyrus and ameliorated behavioral deficits. Alcohol-dependent patients are subjected to disulfiram-treatment to discourage alcohol-consumption. In such patients, enhancement of ADAM10 by disulfiram-treatment was demonstrated in peripheral blood cells. Our data suggest that disulfiram could be repurposed as an ADAM10 enhancer and AD therapeutic. However, efficacy and safety has to be analyzed in Alzheimer patients in the future.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Reinhardt, S., Stoye, N., Luderer, M., Kiefer, F., Schmitt, U., Lieb, K., et al. (2018). Identification of disulfiram as a secretase-modulating compound with beneficial effects on Alzheimer's disease hallmarks. Scientific reports. https://doi.org/10.1038/s41598-018-19577-7
Vancouver
Reinhardt S, Stoye N, Luderer M, Kiefer F, Schmitt U, Lieb K, et al. Identification of disulfiram as a secretase-modulating compound with beneficial effects on Alzheimer's disease hallmarks. Scientific reports. 2018. doi:10.1038/s41598-018-19577-7. PMID: 29358714.
BibTeX
@article{reinhardt2018-29358714,
author = {Reinhardt, S. and Stoye, N. and Luderer, M. and Kiefer, F. and Schmitt, U. and Lieb, K. and Endres, K.},
title = {{Identification of disulfiram as a secretase-modulating compound with beneficial effects on Alzheimer's disease hallmarks}},
journal = {Scientific reports},
year = {2018},
doi = {10.1038/s41598-018-19577-7},
pmid = {29358714},
url = {https://doi.org/10.1038/s41598-018-19577-7}
}
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.
Key findings
- Its enzymatic activity results in secretion of a neuroprotective APP cleavage product (sAPP-alpha) and prevents formation of the amyloidogenic A-beta peptides, major hallmarks of Alzheimer's disease (AD).
- In such patients, enhancement of ADAM10 by disulfiram-treatment was demonstrated in peripheral blood cells.
- Our data suggest that disulfiram could be repurposed as an ADAM10 enhancer and AD therapeutic.
Why it matters
Screening a library of FDA-approved drugs, researchers found that disulfiram, a medicine used for alcohol dependence, boosted ADAM10, an enzyme that steers the amyloid precursor protein away from forming amyloid-beta. In human nerve cells it raised ADAM10 and protective sAPP-alpha, and in Alzheimer model mice it reduced plaque in part of the hippocampus and eased behavioral problems. The authors suggest disulfiram could be repurposed for Alzheimer's, but say its efficacy and safety still have to be tested in Alzheimer patients.
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Study details
- Evidence strengthLow
How this study scored 46/100
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.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Scientific reports) |
| Journal's citation record | 3 / 4 | Scientific Reports: journal h-index 463 (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 | 2 / 5 | 2018 — within 10 year(s) of the newest study here |
| 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 | 3 / 3 | Studied in people (pubmed indexes it as a clinical or observational study) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 55 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.5 citations a year over 10 year(s) since 2018 |
| Impact for its field and year | 3 / 6 | Cited 3.1× 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 | 2 / 4 | Cited 19 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Kristina Endres: h-index 38 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Heidelberg University: institution h-index 1,344 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 29358714) |
| Free to read | 2 / 2 | Free to read |
| Total | 46 / 100 | — |
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Read the original
- DOI: 10.1038/s41598-018-19577-7
- PubMed: 29358714
- Original source →
- Free full text: Scientific Reports →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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