Cholesterol modulates alpha-secretase cleavage of amyloid precursor protein
Bodovitz S, Klein WL.. The Journal of biological chemistry, 1996-02-01
Topic: Brain proteins, microglia and lab models
Amyloid precursor protein (APP) and cholesterol metabolism are genetically linked to Alzheimer's disease, the latter through apolipoprotein E, a lipid and cholesterol transport protein. We have examined the hypothesis that the processing of APP is disrupted by elevated cholesterol, which is known to modulate the activity of several transmembrane proteins. In the current study, cholesterol, solubilized by methyl- beta-cyclodextrin or ethanol, was added to the culture media of APP 751 stably transfected HEK 293 cells. Radiolabeled APP and APPsol (the soluble N-terminal derivative following alpha-secretase cleavage) were precipitated from lysates and conditioned media of stably transfected HEK 293 cells; the relative levels were determined by quantitative densitometry following separation by SDS-polyacrylamide gel electrophoresis. The data show that cholesterol, solubilized by methyl-beta-cyclodextrin, greatly reduced the levels of APPsol. Low doses of ethanol-solubilized cholesterol similarly caused a dramatic reduction of APPsol. By contrast, levels of APP holoprotein remained the same or increased. The large decrease seen in APPsol production was not due to nonspecific inhibition of secretion because several secreted proteins increased in level. Cholesterol, which impedes membrane fluidity, may lower APPsol production by impeding the interaction of the substrate with its protease(s). If APPsol were to function trophically, as suggested by other studies, the current conclusion suggests that changes in cellular cholesterol levels in Alzheimer's disease could contribute to neuronal degeneration by decreasing the production of APPsol.
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APA 7th
Bodovitz, S., & Klein, W. L. (1996). Cholesterol modulates alpha-secretase cleavage of amyloid precursor protein. The Journal of biological chemistry. https://doi.org/10.1074/jbc.271.8.4436
Vancouver
Bodovitz S, Klein WL. Cholesterol modulates alpha-secretase cleavage of amyloid precursor protein. The Journal of biological chemistry. 1996. doi:10.1074/jbc.271.8.4436. PMID: 8626795.
BibTeX
@article{bodovitz1996-8626795,
author = {Bodovitz, S. and Klein, W. L.},
title = {{Cholesterol modulates alpha-secretase cleavage of amyloid precursor protein}},
journal = {The Journal of biological chemistry},
year = {1996},
doi = {10.1074/jbc.271.8.4436},
pmid = {8626795},
url = {https://doi.org/10.1074/jbc.271.8.4436}
}
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Key findings
- If APPsol were to function trophically, as suggested by other studies, the current conclusion suggests that changes in cellular cholesterol levels in Alzheimer's disease could contribute to neuronal degeneration by decreasing the production of APPsol.
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Study details
- Evidence strengthLow
How this study scored 36/100
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. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 21 of the 58 points we could judge it on, which is 36 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The Journal of biological chemistry) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 1996 — 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 8626795) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 21 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 21 of the 58 points we could judge it on is 36 out of 100. |
| Total | 36 / 100 | — |
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