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Small-molecule induction of Aβ-42 peptide production in human cerebral organoids to model Alzheimer's disease associated phenotypes
Pavoni S, Jarray R, Nassor F, Guyot AC, Cottin S, Rontard J, Mikol J, Mabondzo A et al.. PloS one, 2018-12-17
Topic: Disease mechanisms in lab and animal studies
Human mini-brains (MB) are cerebral organoids that recapitulate in part the complexity of the human brain in a unique three-dimensional in vitro model, yielding discrete brain regions reminiscent of the cerebral cortex. Specific proteins linked to neurodegenerative disorders are physiologically expressed in MBs, such as APP-derived amyloids (Aβ), whose physiological and pathological roles and interactions with other proteins are not well established in humans. Here, we demonstrate that neuroectodermal organoids can be used to study the Aβ accumulation implicated in Alzheimer's disease (AD). To enhance the process of protein secretion and accumulation, we adopted a chemical strategy of induction to modulate post-translational pathways of APP using an Amyloid-β Forty-Two Inducer named Aftin-5. Secreted, soluble Aβ fragment concentrations were analyzed in MB-conditioned media. An increase in the Aβ42 fragment secretion was observed as was an increased Aβ42/Aβ40 ratio after drug treatment, which is consistent with the pathological-like phenotypes described in vivo in transgenic animal models and in vitro in induced pluripotent stem cell-derived neural cultures obtained from AD patients. Notably in this context we observe time-dependent Aβ accumulation, which differs from protein accumulation occurring after treatment. We show that mini-brains obtained from a non-AD control cell line are responsive to chemical compound induction, producing a shift of physiological Aβ concentrations, suggesting that this model can be used to identify environmental agents that may initiate the cascade of events ultimately leading to sporadic AD. Increases in both Aβ oligomers and their target, the cellular prion protein (PrPC), support the possibility of using MBs to further understand the pathophysiological role that underlies their interaction in a human model. Finally, the potential application of MBs for modeling age-associated phenotypes and the study of neurological disorders is confirmed.
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APA 7th
Pavoni, S., Jarray, R., Nassor, F., Guyot, A. C., Cottin, S., Rontard, J., et al. (2018). Small-molecule induction of Aβ-42 peptide production in human cerebral organoids to model Alzheimer's disease associated phenotypes. PloS one. https://doi.org/10.1371/journal.pone.0209150
Vancouver
Pavoni S, Jarray R, Nassor F, Guyot AC, Cottin S, Rontard J, et al. Small-molecule induction of Aβ-42 peptide production in human cerebral organoids to model Alzheimer's disease associated phenotypes. PloS one. 2018. doi:10.1371/journal.pone.0209150. PMID: 30557391.
BibTeX
@article{pavoni2018-30557391,
author = {Pavoni, S. and Jarray, R. and Nassor, F. and Guyot, A. C. and Cottin, S. and Rontard, J. and Mikol, J. and Mabondzo, A. and others},
title = {{Small-molecule induction of Aβ-42 peptide production in human cerebral organoids to model Alzheimer's disease associated phenotypes}},
journal = {PloS one},
year = {2018},
doi = {10.1371/journal.pone.0209150},
pmid = {30557391},
url = {https://doi.org/10.1371/journal.pone.0209150}
}
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Key findings
- We show that mini-brains obtained from a non-AD control cell line are responsive to chemical compound induction, producing a shift of physiological Aβ concentrations, suggesting that this model can be used to identify environmental agents that may initiate the cascade of events ultimately leading to sporadic AD.
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Study details
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomized / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 24 of the 58 points we could judge it on, which is 41 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (PloS one) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 2018 — 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 “organoids”) — scores zero |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 30557391) |
| Free to read | 2 / 2 | Free to read |
| Points | 24 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 24 of the 58 points we could judge it on is 41 out of 100. |
| Total | 41 / 100 | — |
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