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Plasma proteomics for cognitive decline and dementia—A Southeast Asian cohort study
Ming Ann Sim, James D. Doecke, Oi Wah Liew, Lee Lee Wong, Eugene S.J. Tan, Siew Pang Chan, Joyce Ruifen Chong, Yuan Cai et al.. Alzheimer s & Dementia, 2025-02-01
Topic: Brain proteins, microglia and lab models
Of 1441 plasma proteins surveyed, a 12-protein signature significantly predicted cognitive decline (q-value < .05). Sixteen diverse biological processes were implicated in cognitive decline. Ten proteins independently predicted incident dementia (q-value < .05). A unified prediction model combining plasma proteins with clinical risk factors increased the area under the curve for outcome prediction from 0.62 to 0.85. External validation in the cerebrospinal fluid proteome of an independent Caucasian cohort replicated four of the significantly predictive plasma markers for cognitive decline namely: GFAP, NEFL, AREG, and PPY. The prognostic proteins prioritized in our study provide robust signals in two different biological matrices, representing potential mechanistic targets for dementia and cognitive decline. HIGHLIGHTS: A total of 1441 plasma proteins were profiled in a Singaporean memory clinic cohort. We report prognostic plasma protein signatures for cognitive decline and dementia. External validation was performed in the cerebrospinal fluid proteome of a Caucasian cohort. A concordant proteomic signature was identified across both biofluids and cohorts. Further studies are needed to explore the therapeutic implications of these proteins for dementia.
Key findings
- Of 1441 plasma proteins surveyed, a 12-protein signature significantly predicted cognitive decline (q-value < .05).
- Sixteen diverse biological processes were implicated in cognitive decline.
- Ten proteins independently predicted incident dementia (q-value < .05).
- A unified prediction model combining plasma proteins with clinical risk factors increased the area under the curve for outcome prediction from 0.62 to 0.85.
- External validation in the cerebrospinal fluid proteome of an independent Caucasian cohort replicated four of the significantly predictive plasma markers for cognitive decline namely: GFAP, NEFL, AREG, and PPY.
Why it matters
A 12-protein plasma signature significantly predicted cognitive decline, and ten proteins independently predicted incident dementia, with a combined model improving prediction. Four markers were replicated in an independent cohort's cerebrospinal fluid, but further studies are needed to explore therapeutic implications.
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Study details
- Participants300
- Evidence strengthModerate
How this study scored 54/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer s & Dementia) |
| Journal's citation record | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (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 | 3 / 5 | Rated “moderate” 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 | 2 / 4 | 300 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 3 / 7 | Cited 21 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 7.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 4 / 6 | Cited 13.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 2 / 4 | Cited 21 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Christopher Chen: h-index 90 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | The University of Melbourne: institution h-index 1,342 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 12 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39998981) |
| Free to read | 2 / 2 | Free to read |
| Total | 54 / 100 | — |
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Read the original
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
Sim, M. A., Doecke, J. D., Liew, O. W., Wong, L. L., Tan, E. S., Chan, S. P., et al. (2025). Plasma proteomics for cognitive decline and dementia—A Southeast Asian cohort study. Alzheimer s & Dementia. https://doi.org/10.1002/alz.14577
Vancouver
Sim MA, Doecke JD, Liew OW, Wong LL, Tan ES, Chan SP, et al. Plasma proteomics for cognitive decline and dementia—A Southeast Asian cohort study. Alzheimer s & Dementia. 2025. doi:10.1002/alz.14577. PMID: 39998981.
BibTeX
@article{sim2025-39998981,
author = {Sim, Ming Ann and Doecke, James D. and Liew, Oi Wah and Wong, Lee Lee and Tan, Eugene S.J. and Chan, Siew Pang and Chong, Joyce Ruifen and Cai, Yuan and others},
title = {{Plasma proteomics for cognitive decline and dementia—A Southeast Asian cohort study}},
journal = {Alzheimer s \& Dementia},
year = {2025},
doi = {10.1002/alz.14577},
pmid = {39998981},
url = {https://doi.org/10.1002/alz.14577}
}
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