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Differential processing of amyloid-beta precursor protein directs human embryonic stem cell proliferation and differentiation into neuronal precursor cells
Porayette P, Gallego MJ, Kaltcheva MM, Bowen RL, Vadakkadath Meethal S, Atwood CS.. The Journal of biological chemistry, 2009-06-19
Topic: Brain proteins, microglia and lab models
The amyloid-beta precursor protein (AbetaPP) is a ubiquitously expressed transmembrane protein whose cleavage product, the amyloid-beta (Abeta) protein, is deposited in amyloid plaques in neurodegenerative conditions such as Alzheimer disease, Down syndrome, and head injury. We recently reported that this protein, normally associated with neurodegenerative conditions, is expressed by human embryonic stem cells (hESCs). We now report that the differential processing of AbetaPP via secretase enzymes regulates the proliferation and differentiation of hESCs. hESCs endogenously produce amyloid-beta, which when added exogenously in soluble and fibrillar forms but not oligomeric forms markedly increased hESC proliferation. The inhibition of AbetaPP cleavage by beta-secretase inhibitors significantly suppressed hESC proliferation and promoted nestin expression, an early marker of neural precursor cell (NPC) formation. The induction of NPC differentiation via the non-amyloidogenic pathway was confirmed by the addition of secreted AbetaPPalpha, which suppressed hESC proliferation and promoted the formation of NPCs. Together these data suggest that differential processing of AbetaPP is normally required for embryonic neurogenesis.
Key findings
- We recently reported that this protein, normally associated with neurodegenerative conditions, is expressed by human embryonic stem cells (hESCs).
- The inhibition of AbetaPP cleavage by beta-secretase inhibitors significantly suppressed hESC proliferation and promoted nestin expression, an early marker of neural precursor cell (NPC) formation.
- Together these data suggest that differential processing of AbetaPP is normally required for embryonic neurogenesis.
Why it matters
This laboratory study of human embryonic stem cells found that blocking cleavage of amyloid precursor protein reduced cell proliferation and promoted early neural precursor formation. These are cells in a dish, not people, so it says nothing yet about treating, curing or preventing Alzheimer's disease.
Study details
- Evidence strengthLow
How this study scored 42/100
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 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 | 2009 — within 20 year(s) of the newest study here |
| 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 | 4 / 7 | Cited 61 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 3.2 citations a year over 19 year(s) since 2009 |
| Impact for its field and year | 3 / 6 | Cited 3.6× 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 3 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Craig Atwood: h-index 64 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Wisconsin–Madison: institution h-index 1,518 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 19542221) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 42 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1074/jbc.m109.026328
- PubMed: 19542221
- 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).
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. Check the citation against the original before you use it.
APA 7th
Porayette, P., Gallego, M. J., Kaltcheva, M. M., Bowen, R. L., Vadakkadath Meethal, S., & Atwood, C. S. (2009). Differential processing of amyloid-beta precursor protein directs human embryonic stem cell proliferation and differentiation into neuronal precursor cells. The Journal of biological chemistry. https://doi.org/10.1074/jbc.m109.026328
Vancouver
Porayette P, Gallego MJ, Kaltcheva MM, Bowen RL, Vadakkadath Meethal S, Atwood CS. Differential processing of amyloid-beta precursor protein directs human embryonic stem cell proliferation and differentiation into neuronal precursor cells. The Journal of biological chemistry. 2009. doi:10.1074/jbc.m109.026328. PMID: 19542221.
BibTeX
@article{porayette2009-19542221,
author = {Porayette, P. and Gallego, M. J. and Kaltcheva, M. M. and Bowen, R. L. and Vadakkadath Meethal, S. and Atwood, C. S.},
title = {{Differential processing of amyloid-beta precursor protein directs human embryonic stem cell proliferation and differentiation into neuronal precursor cells}},
journal = {The Journal of biological chemistry},
year = {2009},
doi = {10.1074/jbc.m109.026328},
pmid = {19542221},
url = {https://doi.org/10.1074/jbc.m109.026328}
}
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