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PSEN1ΔE9, APPswe, and APOE4 Confer Disparate Phenotypes in Human iPSC-Derived Microglia
Konttinen H, Cabral-da-Silva MEC, Ohtonen S, Wojciechowski S, Shakirzyanova A, Caligola S, Giugno R, Ishchenko Y et al.. Stem cell reports, 2019-09-12
Topic: Brain proteins, microglia and lab models
Here we elucidate the effect of Alzheimer disease (AD)-predisposing genetic backgrounds, APOE4, PSEN1ΔE9, and APPswe, on functionality of human microglia-like cells (iMGLs). We present a physiologically relevant high-yield protocol for producing iMGLs from induced pluripotent stem cells. Differentiation is directed with small molecules through primitive erythromyeloid progenitors to re-create microglial ontogeny from yolk sac.
Key findings
- We present a physiologically relevant high-yield protocol for producing iMGLs from induced pluripotent stem cells.
- Differentiation is directed with small molecules through primitive erythromyeloid progenitors to re-create microglial ontogeny from yolk sac.
- The iMGLs express microglial signature genes and respond to ADP with intracellular Ca 2+ release distinguishing them from macrophages.
- Using 16 iPSC lines from healthy donors, AD patients and isogenic controls, we reveal that the APOE4 genotype has a profound impact on several aspects of microglial functionality, whereas PSEN1ΔE9 and APPswe mutations trigger minor alterations.
Why it matters
This laboratory study used human induced pluripotent stem cell-derived microglia-like cells to examine the effects of the Alzheimer's disease-predisposing genetic backgrounds APOE4, PSEN1ΔE9, and APPswe. It reports no treatment, cure, or prevention for people.
Study details
- Evidence strengthLow
How this study scored 51/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Stem cell reports) |
| Journal's citation record | 1 / 4 | Stem Cell Reports: journal h-index 146 (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 | 2 / 5 | 2019 — within 10 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 | Laboratory or animal study (title names “ipsc”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 193 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 21.4 citations a year over 9 year(s) since 2019 |
| Impact for its field and year | 4 / 6 | Cited 9.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 4 other studies in this library |
| Still being cited | 3 / 4 | Cited 71 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Tarja Malm: h-index 53 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Baylor College of Medicine: institution h-index 1,607 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 15 institution(s) in 5 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 31522977) |
| Free to read | 2 / 2 | Free to read |
| Total | 51 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1016/j.stemcr.2019.08.004
- PubMed: 31522977
- Original source →
- Free full text: Stem Cell Reports →
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
Konttinen, H., Cabral-da-Silva, M. E. C., Ohtonen, S., Wojciechowski, S., Shakirzyanova, A., Caligola, S., et al. (2019). PSEN1ΔE9, APPswe, and APOE4 Confer Disparate Phenotypes in Human iPSC-Derived Microglia. Stem cell reports. https://doi.org/10.1016/j.stemcr.2019.08.004
Vancouver
Konttinen H, Cabral-da-Silva MEC, Ohtonen S, Wojciechowski S, Shakirzyanova A, Caligola S, et al. PSEN1ΔE9, APPswe, and APOE4 Confer Disparate Phenotypes in Human iPSC-Derived Microglia. Stem cell reports. 2019. doi:10.1016/j.stemcr.2019.08.004. PMID: 31522977.
BibTeX
@article{konttinen2019-31522977,
author = {Konttinen, H. and Cabral-da-Silva, M. E. C. and Ohtonen, S. and Wojciechowski, S. and Shakirzyanova, A. and Caligola, S. and Giugno, R. and Ishchenko, Y. and others},
title = {{PSEN1ΔE9, APPswe, and APOE4 Confer Disparate Phenotypes in Human iPSC-Derived Microglia}},
journal = {Stem cell reports},
year = {2019},
doi = {10.1016/j.stemcr.2019.08.004},
pmid = {31522977},
url = {https://doi.org/10.1016/j.stemcr.2019.08.004}
}
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