Home › Research › Risk genes beyond APOE
Endoplasmic reticulum and trans-Golgi network generate distinct populations of Alzheimer beta-amyloid peptides
Greenfield JP, Tsai J, Gouras GK, Hai B, Thinakaran G, Checler F, Sisodia SS, Greengard P et al.. Proceedings of the National Academy of Sciences of the United States of America, 1999-01-01
Topic: Brain proteins, microglia and lab models
The excessive generation and accumulation of 40- and 42-aa beta-amyloid peptides (Abeta40/Abeta42) in selectively vulnerable brain regions is a major neuropathological feature of Alzheimer's disease. Abeta, derived by proteolytic cleavage from the beta-amyloid precursor protein (betaAPP), is normally secreted. However, recent evidence suggests that significant levels of Abeta also may remain inside cells.
Key findings
- Abeta, derived by proteolytic cleavage from the beta-amyloid precursor protein (betaAPP), is normally secreted.
- However, recent evidence suggests that significant levels of Abeta also may remain inside cells.
- Here, we have investigated the subcellular compartments within which distinct amyloid species are generated and the compartments from which they are secreted.
- Three experimental approaches were used: (i) immunofluorescence performed in intact cortical neurons; (ii) sucrose gradient fractionation performed with mouse neuroblastoma cells stably expressing wild-type betaAPP695 (N2a695); and (iii) cell-free reconstitution of Abeta generation and trafficking from N2a695 cells.
Why it matters
Using neurons and cell fractionation, this work found that distinct amyloid beta peptides are generated in the endoplasmic reticulum and the trans-Golgi network. This is basic cell biology about where amyloid is made and does not test a therapy.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Evidence strengthLow
How this study scored 48/100
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 (Proceedings of the National Academy of Sciences of the United States of America) |
| Journal's citation record | 4 / 4 | Proceedings of the National Academy of Sciences: journal h-index 1,167 (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 | 1999 — 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 367 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 12.7 citations a year over 29 year(s) since 1999 |
| Impact for its field and year | 4 / 6 | Cited 11.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 8 other studies in this library |
| Still being cited | 1 / 4 | Cited 14 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Huaxi Xu: h-index 85 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Chicago: institution h-index 1,769 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 9892704) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 48 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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.
APA 7th
Greenfield, J. P., Tsai, J., Gouras, G. K., Hai, B., Thinakaran, G., Checler, F., et al. (1999). Endoplasmic reticulum and trans-Golgi network generate distinct populations of Alzheimer beta-amyloid peptides. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.96.2.742
Vancouver
Greenfield JP, Tsai J, Gouras GK, Hai B, Thinakaran G, Checler F, et al. Endoplasmic reticulum and trans-Golgi network generate distinct populations of Alzheimer beta-amyloid peptides. Proceedings of the National Academy of Sciences of the United States of America. 1999. doi:10.1073/pnas.96.2.742. PMID: 9892704.
BibTeX
@article{greenfield1999-9892704,
author = {Greenfield, J. P. and Tsai, J. and Gouras, G. K. and Hai, B. and Thinakaran, G. and Checler, F. and Sisodia, S. S. and Greengard, P. and others},
title = {{Endoplasmic reticulum and trans-Golgi network generate distinct populations of Alzheimer beta-amyloid peptides}},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {1999},
doi = {10.1073/pnas.96.2.742},
pmid = {9892704},
url = {https://doi.org/10.1073/pnas.96.2.742}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.
Later studies that cite this one
8 studies in the alzhub library list this one in their references.
Related studies in Risk genes beyond APOE
Also tagged “amyloid-beta”
1,339 studies in the library carry the topic tag “amyloid-beta”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 1,339 tagged studies.