Polygenic risk score of Alzheimer's disease is associated with cognitive trajectories and phenotypes of cerebral organoids
Min Young Chun, Sang-Hyuk Jung, Juran Choe, Seung-Yeon Lee, Hang-Rai Kim, Hyo Jin Son, Yejoo Choi, Minyoung Cho et al.. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025-09
Topic: Genetics and APOE
Plain-language summary
OptPRS predicted AD dementia and Aβ positivity, independent of apolipoprotein E (APOE). Higher optPRSs correlated with rapid cognitive decline. Cerebral organoids from the high optPRS group exhibited increased Aβ insolubility and p-tau levels. OptPRS predicted cognitive decline and AD phenotypes of cerebral organoids, supporting its use in risk assessments and drug-screening platform. HIGHLIGHTS: Optimized polygenic risk scores (optPRSs) improve the prediction of Alzheimer's disease (AD) dementia and amyloid beta positivity (Aβ+). High optPRS is associated with faster cognitive decline, particularly in Aβ+. Induced pluripotent stem cell (iPSC)-derived cerebral organoids from high optPRSs show high Aβ insolubility and phosphorylated tau (p-tau). PRS genetic risk stratification provides insight into AD progression and pathology.
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APA 7th
Chun, M. Y., Jung, S.-H., Choe, J., Lee, S.-Y., Kim, H.-R., Son, H. J., et al. (2025). Polygenic risk score of Alzheimer's disease is associated with cognitive trajectories and phenotypes of cerebral organoids. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.70660
Vancouver
Chun MY, Jung S.-H, Choe J, Lee S.-Y, Kim H.-R, Son HJ, et al. Polygenic risk score of Alzheimer's disease is associated with cognitive trajectories and phenotypes of cerebral organoids. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2025. doi:10.1002/alz.70660. PMID: 40959898.
BibTeX
@article{chun2025-40959898,
author = {Chun, Min Young and Jung, Sang-Hyuk and Choe, Juran and Lee, Seung-Yeon and Kim, Hang-Rai and Son, Hyo Jin and Choi, Yejoo and Cho, Minyoung and others},
title = {{Polygenic risk score of Alzheimer's disease is associated with cognitive trajectories and phenotypes of cerebral organoids}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2025},
doi = {10.1002/alz.70660},
pmid = {40959898},
url = {https://doi.org/10.1002/alz.70660}
}
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Key findings
- OptPRS predicted AD dementia and Aβ positivity, independent of apolipoprotein E (APOE).
- Higher optPRSs correlated with rapid cognitive decline.
- Cerebral organoids from the high optPRS group exhibited increased Aβ insolubility and p-tau levels.
- OptPRS predicted cognitive decline and AD phenotypes of cerebral organoids, supporting its use in risk assessments and drug-screening platform.
- HIGHLIGHTS: Optimized polygenic risk scores (optPRSs) improve the prediction of Alzheimer's disease (AD) dementia and amyloid beta positivity (Aβ+).
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Study details
- Participants1,634
- Evidence strengthLow
How this study scored 52/100
Published in a leading specialty journal. Scored zero for study design, 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, multicenter collaboration and free to read, so those were left out: it earned 29 of the 56 points we could judge it on, which is 52 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Alzheimer's & dementia : the journal of the Alzheimer's Association) |
| 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 | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 3 / 4 | 1,634 participants |
| 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 40959898) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 29 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 29 of the 56 points we could judge it on is 52 out of 100. |
| Total | 52 / 100 | — |
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