Home › Research › Biomarkers
Alzheimer's Disease polygenic risk, the plasma proteome, and dementia incidence among UK older adults
May A Beydoun, Hind A Beydoun, Zhiguang Li, Yi-Han Hu, Nicole Noren Hooten, Jun Ding, Sharmin Hossain, Christian A Maino Vieytes et al.. GeroScience, 2024-11-26
Topic: Genetics and APOE
Alzheimer's Disease (AD) is a complex polygenic neurodegenerative disorder. Its genetic risk's relationship with all-cause dementia may be influenced by the plasma proteome. Up to 40,139 UK Biobank participants aged ≥ 50y at baseline assessment (2006-2010) were followed-up for ≤ 15 y for dementia incidence. Plasma proteomics were performed on a sub-sample of UK Biobank participants (k = 1,463 plasma proteins). AD polygenic risk scores (PRS) were used as the primary exposure and Cox proportional hazards models were conducted to examine the AD PRS-dementia relationship. A four-way decomposition model then partitioned the total effect (TE) of AD PRS on dementia into an effect due to mediation only, an effect due to interaction only, neither or both. The study found that AD PRS tertiles significantly increased the risk for all-cause dementia, particularly among women. The study specifically found that AD PRS was associated with a 79% higher risk for all-cause dementia for each unit increase (HR = 1.79, 95% CI: 1.70-1.87, P < 0.001). Eighty-six plasma proteins were significantly predicted by AD PRS, including a positive association with PLA2G7, BRK1, the glial acidic fibrillary protein (GFAP), neurofilament light chain (NfL), and negative with TREM2. Both GFAP and NfL significantly interacted synergistically with AD PRS to increase all-dementia risk (> 10% of TE is pure interaction), while GFAP was also an important consistent mediator in the AD PRS-dementia relationship. In summary, we detected significant interactions of NfL and GFAP with AD PRS, in relation to dementia incidence, suggesting potential for personalized dementia prevention and management.
Key findings
- The study found that AD PRS tertiles significantly increased the risk for all-cause dementia, particularly among women.
- The study specifically found that AD PRS was associated with a 79% higher risk for all-cause dementia for each unit increase (HR = 1.79, 95% CI: 1.70-1.87, P < 0.001).
- Eighty-six plasma proteins were significantly predicted by AD PRS, including a positive association with PLA2G7, BRK1, the glial acidic fibrillary protein (GFAP), neurofilament light chain (NfL), and negative with TREM2.
- Both GFAP and NfL significantly interacted synergistically with AD PRS to increase all-dementia risk (> 10% of TE is pure interaction), while GFAP was also an important consistent mediator in the AD PRS-dementia relationship.
- In summary, we detected significant interactions of NfL and GFAP with AD PRS, in relation to dementia incidence, suggesting potential for personalized dementia prevention and management.
New to this subject? Start with our plain-English guide: Blood tests & biomarkers →
Study details
- Effect sizeHR = 1.79
- Evidence strengthLow
How this study scored 48/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, studied in people and randomised / 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, multi-centre collaboration and free to read, so those were left out: it earned 27 of the 56 points we could judge it on, which is 48 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (GeroScience) |
| 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 | 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 | — / 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 |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39586964) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 27 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 27 of the 56 points we could judge it on is 48 out of 100. |
| Total | 48 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
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
Beydoun, M. A., Beydoun, H. A., Li, Z., Hu, Y.-H., Hooten, N. N., Ding, J., et al. (2025). Alzheimer's Disease polygenic risk, the plasma proteome, and dementia incidence among UK older adults. GeroScience. https://doi.org/10.1007/s11357-024-01413-8
Vancouver
Beydoun MA, Beydoun HA, Li Z, Hu Y.-H, Hooten NN, Ding J, et al. Alzheimer's Disease polygenic risk, the plasma proteome, and dementia incidence among UK older adults. GeroScience. 2025. doi:10.1007/s11357-024-01413-8. PMID: 39586964.
BibTeX
@article{beydoun2025-39586964,
author = {Beydoun, May A and Beydoun, Hind A and Li, Zhiguang and Hu, Yi-Han and Hooten, Nicole Noren and Ding, Jun and Hossain, Sharmin and Vieytes, Christian A Maino and others},
title = {{Alzheimer's Disease polygenic risk, the plasma proteome, and dementia incidence among UK older adults}},
journal = {GeroScience},
year = {2025},
doi = {10.1007/s11357-024-01413-8},
pmid = {39586964},
url = {https://doi.org/10.1007/s11357-024-01413-8}
}