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Plasma levels of beta-amyloid(1-40), beta-amyloid(1-42), and total beta-amyloid remain unaffected in adult patients with hypercholesterolemia after treatment with statins
Höglund K, Wiklund O, Vanderstichele H, Eikenberg O, Vanmechelen E, Blennow K.. Archives of neurology, 2004-03-01
Topic: Amyloid, tau and blood-test diagnosis
Background Epidemiological studies suggest that statins reduce the risk of developing Alzheimer disease. Cell and animal experiments have revealed a connection between cholesterol metabolism and the processing of amyloid precursor protein. To our knowledge, the mechanism for statins in risk reduction of Alzheimer disease is unknown. Objective To test the effect of statin treatment on beta-amyloid (A beta) metabolism in humans. Design A prospective, randomized, dose-finding 36-week treatment trial with statins. Plasma samples were taken at baseline (week 0) and at weeks 6, 12, and 36. Setting Outpatient clinical study at a university hospital. Patients Thirty-nine patients who met the criteria for hypercholesterolemia. Interventions Patients were randomized to oral treatment with either simvastatin or atorvastatin calcium according to the following regimen: simvastatin, 40 mg/d, or atorvastatin, 20 mg/d, for 6 weeks; followed by simvastatin, 80 mg/d, or atorvastatin, 40 mg/d, for 6 weeks; and finally, simvastatin, 80 mg/d, or atorvastatin, 80 mg/d, for 24 weeks. Main outcome measures Plasma levels of A beta(1-40) and A beta(1-42) were measured using 2 enzyme-linked immunosorbent assays, and total A beta was quantified by Western blotting. Results Treatment with both statins reduced total plasma cholesterol levels by 56% (P =.00). The plasma levels of A beta(1-40), A beta(1-42), and total A beta were stable in individual patients during the treatment period. No significant change in the level of A beta(1-40), A beta(1-42), or total A beta was found. Conclusion This study questions the effect of statins on the processing of amyloid precursor protein in humans.
Key findings
- Background Epidemiological studies suggest that statins reduce the risk of developing Alzheimer disease.
- Cell and animal experiments have revealed a connection between cholesterol metabolism and the processing of amyloid precursor protein.
- Results Treatment with both statins reduced total plasma cholesterol levels by 56% (P =.00).
- No significant change in the level of A beta(1-40), A beta(1-42), or total A beta was found.
Why it matters
In 39 patients with high cholesterol, statin treatment lowered cholesterol but did not change plasma levels of beta-amyloid 1-40, beta-amyloid 1-42, or total beta-amyloid. This suggests that statins do not affect amyloid metabolism in the blood, and the study did not test whether statins prevent or treat Alzheimer's disease.
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Study details
- Evidence strengthHigh
How this study scored 62/100
Published in a peer-reviewed journal, and it is a randomised controlled trial. Scored zero for sample size and effect reported because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Archives of neurology) |
| Journal's citation record | 3 / 4 | Archives of Neurology: journal h-index 353 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A randomised controlled trial (from PubMed type “Randomized Controlled Trial”) |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2004 — 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 | 3 / 3 | Studied in people (pubmed indexes it as a clinical or observational study) |
| Randomised / blinded | 1 / 2 | Randomised (as stated in the record) |
| Times cited | 5 / 7 | Cited 104 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.3 citations a year over 24 year(s) since 2004 |
| Impact for its field and year | 4 / 6 | Cited 10.1× 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 7 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Kaj Blennow: h-index 220 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Gothenburg: institution h-index 972 (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 15023808) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 62 / 100 | — |
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APA 7th
Höglund, K., Wiklund, O., Vanderstichele, H., Eikenberg, O., Vanmechelen, E., & Blennow, K. (2004). Plasma levels of beta-amyloid(1-40), beta-amyloid(1-42), and total beta-amyloid remain unaffected in adult patients with hypercholesterolemia after treatment with statins. Archives of neurology. https://doi.org/10.1001/archneur.61.3.333
Vancouver
Höglund K, Wiklund O, Vanderstichele H, Eikenberg O, Vanmechelen E, Blennow K. Plasma levels of beta-amyloid(1-40), beta-amyloid(1-42), and total beta-amyloid remain unaffected in adult patients with hypercholesterolemia after treatment with statins. Archives of neurology. 2004. doi:10.1001/archneur.61.3.333. PMID: 15023808.
BibTeX
@article{hoglund2004-15023808,
author = {Höglund, K. and Wiklund, O. and Vanderstichele, H. and Eikenberg, O. and Vanmechelen, E. and Blennow, K.},
title = {{Plasma levels of beta-amyloid(1-40), beta-amyloid(1-42), and total beta-amyloid remain unaffected in adult patients with hypercholesterolemia after treatment with statins}},
journal = {Archives of neurology},
year = {2004},
doi = {10.1001/archneur.61.3.333},
pmid = {15023808},
url = {https://doi.org/10.1001/archneur.61.3.333}
}
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