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A detergent-insoluble membrane compartment contains A beta in vivo
Lee SJ, Liyanage U, Bickel PE, Xia W, Lansbury PT, Kosik KS.. Nature medicine, 1998-06-01
Topic: Brain proteins, microglia and lab models
Ordered assembly of the amyloid-beta protein (A beta) into amyloid fibrils is a critical step in Alzheimer's disease (AD). To release the amyloidogenic peptide A beta from the Alzheimer amyloid precursor protein (APP), two secretases act sequentially: first, beta-secretase cleaves close to the membrane within the ectodomain and then gamma-secretase cuts within the transmembrane domain. The sites of gamma-secretase cleavage are after residues 40 or 42 of A beta.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Lee, S. J., Liyanage, U., Bickel, P. E., Xia, W., Lansbury, P. T., & Kosik, K. S. (1998). A detergent-insoluble membrane compartment contains A beta in vivo. Nature medicine. https://doi.org/10.1038/nm0698-730
Vancouver
Lee SJ, Liyanage U, Bickel PE, Xia W, Lansbury PT, Kosik KS. A detergent-insoluble membrane compartment contains A beta in vivo. Nature medicine. 1998. doi:10.1038/nm0698-730. PMID: 9623986.
BibTeX
@article{lee1998-9623986,
author = {Lee, S. J. and Liyanage, U. and Bickel, P. E. and Xia, W. and Lansbury, P. T. and Kosik, K. S.},
title = {{A detergent-insoluble membrane compartment contains A beta in vivo}},
journal = {Nature medicine},
year = {1998},
doi = {10.1038/nm0698-730},
pmid = {9623986},
url = {https://doi.org/10.1038/nm0698-730}
}
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Key findings
- To release the amyloidogenic peptide A beta from the Alzheimer amyloid precursor protein (APP), two secretases act sequentially: first, beta-secretase cleaves close to the membrane within the ectodomain and then gamma-secretase cuts within the transmembrane domain.
- The sites of gamma-secretase cleavage are after residues 40 or 42 of A beta.
- Except in those rare cases of AD caused by a mutation, levels of secreted A beta are not elevated; thus, the secretory pathway may be unaffected, and factors other than the extracellular concentration of A beta may contribute to the aggregation properties of the peptide.
- A beta is also present in intracellular compartments.
Why it matters
This study found that A beta is present in a detergent-insoluble membrane compartment in vivo and that secreted A beta levels are not elevated except in rare mutation-caused Alzheimer's disease. It describes where A beta is located but does not provide a treatment, cure, or prevention.
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Study details
- Evidence strengthLow
How this study scored 53/100
Published in a top-tier 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 | 10 / 10 | Tier 1 — top-tier general journal (Nature medicine) |
| Journal's citation record | 4 / 4 | Nature Medicine: journal h-index 763 (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 | 1998 — 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 | 6 / 7 | Cited 396 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 13.2 citations a year over 30 year(s) since 1998 |
| Impact for its field and year | 4 / 6 | Cited 16.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 5 other studies in this library |
| Still being cited | 1 / 4 | Cited 9 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Kenneth S. Kosik: h-index 108 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 9623986) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 53 / 100 | — |
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