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The low density lipoprotein receptor-related protein (LRP) is a novel beta-secretase (BACE1) substrate
von Arnim CA, Kinoshita A, Peltan ID, Tangredi MM, Herl L, Lee BM, Spoelgen R, Hshieh TT et al.. The Journal of biological chemistry, 2005-03-04
Topic: Brain proteins, microglia and lab models
BACE is a transmembrane protease with beta-secretase activity that cleaves the amyloid precursor protein (APP). After BACE cleavage, APP becomes a substrate for gamma-secretase, leading to release of amyloid-beta peptide (Abeta), which accumulates in senile plaques in Alzheimer disease. APP and BACE are co-internalized from the cell surface to early endosomes.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
von Arnim, C. A., Kinoshita, A., Peltan, I. D., Tangredi, M. M., Herl, L., Lee, B. M., et al. (2005). The low density lipoprotein receptor-related protein (LRP) is a novel beta-secretase (BACE1) substrate. The Journal of biological chemistry. https://doi.org/10.1074/jbc.m414248200
Vancouver
von Arnim CA, Kinoshita A, Peltan ID, Tangredi MM, Herl L, Lee BM, et al. The low density lipoprotein receptor-related protein (LRP) is a novel beta-secretase (BACE1) substrate. The Journal of biological chemistry. 2005. doi:10.1074/jbc.m414248200. PMID: 15749709.
BibTeX
@article{vonarnim2005-15749709,
author = {von Arnim, C. A. and Kinoshita, A. and Peltan, I. D. and Tangredi, M. M. and Herl, L. and Lee, B. M. and Spoelgen, R. and Hshieh, T. T. and others},
title = {{The low density lipoprotein receptor-related protein (LRP) is a novel beta-secretase (BACE1) substrate}},
journal = {The Journal of biological chemistry},
year = {2005},
doi = {10.1074/jbc.m414248200},
pmid = {15749709},
url = {https://doi.org/10.1074/jbc.m414248200}
}
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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- After BACE cleavage, APP becomes a substrate for gamma-secretase, leading to release of amyloid-beta peptide (Abeta), which accumulates in senile plaques in Alzheimer disease.
- APP and BACE are co-internalized from the cell surface to early endosomes.
- APP is also known to interact at the cell surface and be internalized by the low density lipoprotein receptor-related protein (LRP), a multifunctional endocytic and signaling receptor.
- Using a new fluorescence resonance energy transfer (FRET)-based assay of protein proximity, fluorescence lifetime imaging (FLIM), and co-immunoprecipitation we demonstrate that the light chain of LRP interacts with BACE on the cell surface in association with lipid rafts.
Why it matters
In laboratory experiments using protein-proximity imaging (FRET/FLIM) and co-immunoprecipitation, this study found that the light chain of the receptor LRP "interacts with BACE on the cell surface in association with lipid rafts," and reports LRP as a new substrate of BACE1, the enzyme that starts amyloid-beta production from APP. This means BACE1 acts on more than APP. The study does not test any treatment or measure any effect on Alzheimer's disease in people.
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Study details
- Evidence strengthLow
How this study scored 49/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 257 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 11.2 citations a year over 23 year(s) since 2005 |
| Impact for its field and year | 4 / 6 | Cited 12.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 10 other studies in this library |
| Still being cited | 1 / 4 | Cited 13 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Bradley T. Hyman: h-index 190 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multicenter collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 15749709) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 49 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1074/jbc.m414248200
- PubMed: 15749709
- 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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