A multiancestry polygenic risk score for Alzheimer's disease is associated with cognitive decline and neuropathological hallmarks in diverse populations
Kurniansyah N, Tasaki S, Rehman H, Zhu C, Farrell J, Sherva R, Hauger R, Merritt VC, Panizzon M, Zhang R, Gaziano JM, Gim J, et al.. Nature genetics, 2026-08-27
Topic: Amyloid, tau and blood-test diagnosis
Previously derived polygenic risk scores (PRSs) for Alzheimer's disease (AD) perform inconsistently across diverse ancestries. We developed an APOE-independent multiancestry AD PRS using genome-wide association study summary statistics applied to European ancestry, African American, Caribbean Hispanic and East Asian cohorts. PRS performance was evaluated in a large independent multiancestry dataset and validated in several additional multiancestry cohorts. The PRS was significantly associated with AD in European ancestry, African American, Caribbean Hispanic and Native American Hispanic groups with adjusted odds ratios between 1.14 and 1.52 per PRS standard deviation. PRS performance was validated in the replication cohorts (odds ratios: 1.21-1.65). The PRS was also associated with poorer memory, executive function and language performance, greater AD-related neuropathological burden, reduced hippocampal volume, lower cerebrospinal fluid amyloid-β 42 and elevated total tau and phosphorylated tau, with stronger phosphorylated tau associations observed in women. Our findings support the value of ancestry-aware PRSs as a component of broader multimodal risk stratification frameworks.
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APA 7th
Kurniansyah, N., Tasaki, S., Rehman, H., Zhu, C., Farrell, J., Sherva, R., et al. (2026). A multiancestry polygenic risk score for Alzheimer's disease is associated with cognitive decline and neuropathological hallmarks in diverse populations. Nature genetics. https://doi.org/10.1038/s41588-026-02722-8
Vancouver
Kurniansyah N, Tasaki S, Rehman H, Zhu C, Farrell J, Sherva R, et al. A multiancestry polygenic risk score for Alzheimer's disease is associated with cognitive decline and neuropathological hallmarks in diverse populations. Nature genetics. 2026. doi:10.1038/s41588-026-02722-8. PMID: 42661068.
BibTeX
@article{kurniansyah2026-42661068,
author = {Kurniansyah, N. and Tasaki, S. and Rehman, H. and Zhu, C. and Farrell, J. and Sherva, R. and Hauger, R. and Merritt, V. C. and Panizzon, M. and Zhang, R. and Gaziano, J. M. and Gim, J. and others},
title = {{A multiancestry polygenic risk score for Alzheimer's disease is associated with cognitive decline and neuropathological hallmarks in diverse populations}},
journal = {Nature genetics},
year = {2026},
doi = {10.1038/s41588-026-02722-8},
pmid = {42661068},
url = {https://doi.org/10.1038/s41588-026-02722-8}
}
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Key findings
- The PRS was significantly associated with AD in European ancestry, African American, Caribbean Hispanic and Native American Hispanic groups with adjusted odds ratios between 1.14 and 1.52 per PRS standard deviation.
- The PRS was also associated with poorer memory, executive function and language performance, greater AD-related neuropathological burden, reduced hippocampal volume, lower cerebrospinal fluid amyloid-β 42 and elevated total tau and phosphorylated tau, with stronger phosphorylated tau associations observed in women.
- Our findings support the value of ancestry-aware PRSs as a component of broader multimodal risk stratification frameworks.
Why it matters
A polygenic risk score built for multiple ancestries was linked to Alzheimer's diagnosis, worse memory and thinking, and more disease-related brain changes. This is a risk-stratification tool, not a way to treat, cure or prevent the disease.
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Study details
- Study designcohort
- Effect sizeOR 1.14-1.52 per PRS SD across ancestry groups; 1.21-1.65 in replication cohorts
- Evidence strengthHigh
Limitations
Non-European populations were under-represented in both discovery and validation datasets and ancestry-specific GWAS were absent for Native American Hispanic and Caribbean Hispanic groups; reliance on ICD codes for case ascertainment in Million Veteran Program, FinnGen and All of Us may have limited diagnostic accuracy; clinically diagnosed AD is not equivalent to biologically confirmed AD; and several non-European datasets had modest power for ancestry- or sex-specific effects.
How this study scored 56/100
Published in a leading specialty journal, and it is a cohort study following people over time. Scored zero for sample size, studied in people and randomised / blinded because the record does not state it. We have no data on free to read, so that was left out: it earned 55 of the 98 points we could judge it on, which is 56 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature genetics) |
| Journal's citation record | 4 / 4 | Nature Genetics: journal h-index 776 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A cohort study following people over time |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 5 / 5 | 2026 — within 1 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 | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| 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 | 0 / 7 | Cited 0 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.0 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 0 / 6 | Cited 0.0× 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 | 0 / 4 | Cited 0 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Lindsay A. Farrer: h-index 119 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 26 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 42661068) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 55 / 98 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 55 of the 98 points we could judge it on is 56 out of 100. |
| Total | 56 / 100 | — |
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