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The neurodegeneration mutant löchrig interferes with cholesterol homeostasis and Appl processing
Tschäpe JA, Hammerschmied C, Mühlig-Versen M, Athenstaedt K, Daum G, Kretzschmar D.. The EMBO journal, 2002-12-01
Topic: Brain proteins, microglia and lab models
The novel Drosophila mutant löchrig (loe) shows progressive neurodegeneration and neuronal cell death, in addition to a low level of cholesterol ester. loe affects a specific isoform of the gamma-subunit of AMP-activated protein kinase (AMPK), a negative regulator of hydroxymethylglutaryl (HMG)-CoA reductase and cholesterol synthesis in vertebrates. Although Drosophila cannot synthesize cholesterol de novo, the regulatory role of fly AMPK on HMG-CoA reductase is conserved. The loe phenotype is modified by the level of HMG-CoA reductase and suppressed by the inhibition of this enzyme by statin, which has been used for the treatment of Alzheimer patients.
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APA 7th
Tschäpe, J. A., Hammerschmied, C., Mühlig-Versen, M., Athenstaedt, K., Daum, G., & Kretzschmar, D. (2002). The neurodegeneration mutant löchrig interferes with cholesterol homeostasis and Appl processing. The EMBO journal. https://doi.org/10.1093/emboj/cdf636
Vancouver
Tschäpe JA, Hammerschmied C, Mühlig-Versen M, Athenstaedt K, Daum G, Kretzschmar D. The neurodegeneration mutant löchrig interferes with cholesterol homeostasis and Appl processing. The EMBO journal. 2002. doi:10.1093/emboj/cdf636. PMID: 12456644.
BibTeX
@article{tschape2002-12456644,
author = {Tschäpe, J. A. and Hammerschmied, C. and Mühlig-Versen, M. and Athenstaedt, K. and Daum, G. and Kretzschmar, D.},
title = {{The neurodegeneration mutant löchrig interferes with cholesterol homeostasis and Appl processing}},
journal = {The EMBO journal},
year = {2002},
doi = {10.1093/emboj/cdf636},
pmid = {12456644},
url = {https://doi.org/10.1093/emboj/cdf636}
}
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Key findings
- Although Drosophila cannot synthesize cholesterol de novo, the regulatory role of fly AMPK on HMG-CoA reductase is conserved.
- The loe phenotype is modified by the level of HMG-CoA reductase and suppressed by the inhibition of this enzyme by statin, which has been used for the treatment of Alzheimer patients.
- In addition, the degenerative phenotype of loe is enhanced by a mutation in amyloid precursor protein-like (APPL), the fly homolog of the human amyloid precursor protein involved in Alzheimer's disease.
- Western analysis revealed that the loe mutation reduces APPL processing, whereas overexpression of Loe increases it.
Why it matters
In a Drosophila mutant, the neurodegenerative phenotype was modified by HMG-CoA reductase levels and suppressed by statin, and enhanced by a mutation in the fly amyloid precursor protein-like gene. This is a fruit fly study and does not show any treatment, cure, or prevention for Alzheimer's disease in humans.
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Study details
- Evidence strengthLow
How this study scored 40/100
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 EMBO journal) |
| Journal's citation record | 4 / 4 | The EMBO Journal: journal h-index 563 (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 | 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 | 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 128 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.9 citations a year over 26 year(s) since 2002 |
| Impact for its field and year | 3 / 6 | Cited 3.7× 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 | 1 / 4 | Cited 6 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Doris Kretzschmar: h-index 33 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Würzburg: institution h-index 852 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 12456644) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 40 / 100 | — |
What each of these 20 components measures, and what this score is not →
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