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Statins cause intracellular accumulation of amyloid precursor protein, beta-secretase-cleaved fragments, and amyloid beta-peptide via an isoprenoid-dependent mechanism
Cole SL, Grudzien A, Manhart IO, Kelly BL, Oakley H, Vassar R.. The Journal of biological chemistry, 2005-02-17
Topic: Brain proteins, microglia and lab models
The use of statins, 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors that block the synthesis of mevalonate (and downstream products such as cholesterol and nonsterol isoprenoids), as a therapy for Alzheimer disease is currently the subject of intense debate. It has been reported that statins reduce the risk of developing the disorder, and a link between cholesterol and Alzheimer disease pathophysiology has been proposed. Moreover, experimental studies focusing on the cholesterol-dependent effects of statins have demonstrated a close association between cellular cholesterol levels and amyloid production.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Cole, S. L., Grudzien, A., Manhart, I. O., Kelly, B. L., Oakley, H., & Vassar, R. (2005). Statins cause intracellular accumulation of amyloid precursor protein, beta-secretase-cleaved fragments, and amyloid beta-peptide via an isoprenoid-dependent mechanism. The Journal of biological chemistry. https://doi.org/10.1074/jbc.m413895200
Vancouver
Cole SL, Grudzien A, Manhart IO, Kelly BL, Oakley H, Vassar R. Statins cause intracellular accumulation of amyloid precursor protein, beta-secretase-cleaved fragments, and amyloid beta-peptide via an isoprenoid-dependent mechanism. The Journal of biological chemistry. 2005. doi:10.1074/jbc.m413895200. PMID: 15718241.
BibTeX
@article{cole2005-15718241,
author = {Cole, S. L. and Grudzien, A. and Manhart, I. O. and Kelly, B. L. and Oakley, H. and Vassar, R.},
title = {{Statins cause intracellular accumulation of amyloid precursor protein, beta-secretase-cleaved fragments, and amyloid beta-peptide via an isoprenoid-dependent mechanism}},
journal = {The Journal of biological chemistry},
year = {2005},
doi = {10.1074/jbc.m413895200},
pmid = {15718241},
url = {https://doi.org/10.1074/jbc.m413895200}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
Key findings
- It has been reported that statins reduce the risk of developing the disorder, and a link between cholesterol and Alzheimer disease pathophysiology has been proposed.
- Moreover, experimental studies focusing on the cholesterol-dependent effects of statins have demonstrated a close association between cellular cholesterol levels and amyloid production.
- However, evidence suggests that statins are pleiotropic, and the potential cholesterol-independent effects of statins on amyloid precursor protein (APP) metabolism and amyloid beta-peptide (A beta) genesis are unknown.
- In this study, we developed a novel in vitro system that enabled the discrete analysis of cholesterol-dependent and -independent (i.e. isoprenoid-dependent) statin effects on APP cleavage and A beta formation.
Why it matters
This laboratory study found that statins cause intracellular accumulation of amyloid precursor protein, beta-secretase-cleaved fragments, and amyloid beta-peptide through an isoprenoid-dependent mechanism. This complicates the idea that statins protect against Alzheimer's disease, but it is cell-based work and does not establish what happens in patients.
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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 (The Journal of biological chemistry) |
| Journal's citation record | 4 / 4 | Journal of Biological Chemistry: journal h-index 780 (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 | 2005 — 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 135 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.9 citations a year over 23 year(s) since 2005 |
| Impact for its field and year | 4 / 6 | Cited 9.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 7 other studies in this library |
| Still being cited | 1 / 4 | Cited 3 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Robert J. Vassar: h-index 73 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Northwestern University: institution h-index 1,592 (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 15718241) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 44 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1074/jbc.m413895200
- PubMed: 15718241
- Original source →
- Free full text: Journal of Biological Chemistry →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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