Associations of circulating c-reactive protein levels with central Alzheimer’s disease biomarkers
Hyeji Choi, Min Soo Byun, Dahyun Yi, Hyejin Ahn, Gijung Jung, Sang‐Yong Park, Joon Hyung Jung, Musung Keum et al.. The Journal of Prevention of Alzheimer s Disease, 2025-09-17
Topic: Amyloid, tau and blood-test diagnosis
The mean (SD) age of participants was 70.57 (8.00) years, with 179 (42.9 %) females. Circulating CRP levels showed non-linear associations with A/T/N biomarkers of AD, showing a U-shaped relationship with Aβ and tau deposition and an inverted U-shaped association with neurodegeneration. Threshold effect analyses revealed that CRP was inversely associated with Aβ deposition (B = -0.081; 95 % CI, -0.153 to -0.007; p = 0.031) below 0.63 mg/L, after adjusting for all confounding variables. In contrast, higher CRP levels were associated with lower cerebral glucose metabolism in AD-signature regions, indicative of greater AD-related neurodegeneration, when above 2.15 mg/L (B = -0.056; 95 % CI, -0.112 to -0.001; p= 0.042). Our study revealed differential associations between circulating CRP levels and central AD biomarkers that varied according to the CRP concentration. Further studies are necessary to elucidate the mechanisms underlying the inverse relationship between circulating CRP and brain Aβ within the clinically normal range, as well as potential aggravating effects of elevated CRP on Aβ-independent neurodegeneration.
Key findings
- The mean (SD) age of participants was 70.57 (8.00) years, with 179 (42.9 %) females.
- Circulating CRP levels showed non-linear associations with A/T/N biomarkers of AD, showing a U-shaped relationship with Aβ and tau deposition and an inverted U-shaped association with neurodegeneration.
- Threshold effect analyses revealed that CRP was inversely associated with Aβ deposition (B = -0.081; 95 % CI, -0.153 to -0.007; p = 0.031) below 0.63 mg/L, after adjusting for all confounding variables.
- In contrast, higher CRP levels were associated with lower cerebral glucose metabolism in AD-signature regions, indicative of greater AD-related neurodegeneration, when above 2.15 mg/L (B = -0.056; 95 % CI, -0.112 to -0.001; p= 0.042).
- Our study revealed differential associations between circulating CRP levels and central AD biomarkers that varied according to the CRP concentration.
Why it matters
This cross-sectional study found that blood C-reactive protein levels had non-linear, U-shaped relationships with Alzheimer's disease biomarkers, with different effects at low and high levels. Because it is cross-sectional, it cannot show whether these relationships are causal.
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Study details
- Study designcross-sectional
- Participants123
- Evidence strengthLow
How this study scored 46/100
Published in a peer-reviewed journal, and it is a snapshot of people at one point in time. Scored zero for effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The Journal of Prevention of Alzheimer s Disease) |
| Journal's citation record | 0 / 4 | The Journal of Prevention of Alzheimer s Disease: journal h-index 63 (OpenAlex, 2026-10-29) |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| 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 | 2 / 4 | 123 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 | 1 / 7 | Cited 4 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 2.5× 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 | 1 / 4 | Cited 4 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Dong Young Lee: h-index 49 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Seoul National University: institution h-index 1,053 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 10 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40967969) |
| Free to read | 2 / 2 | Free to read |
| Total | 46 / 100 | — |
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Read the original
- DOI: 10.1016/j.tjpad.2025.100368
- PubMed: 40967969
- Original source →
- Free full text: The Journal of Prevention of Alzheimer s Disease →
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
Choi, H., Byun, M. S., Yi, D., Ahn, H., Jung, G., Park, S., et al. (2025). Associations of circulating c-reactive protein levels with central Alzheimer’s disease biomarkers. The Journal of Prevention of Alzheimer s Disease. https://doi.org/10.1016/j.tjpad.2025.100368
Vancouver
Choi H, Byun MS, Yi D, Ahn H, Jung G, Park S, et al. Associations of circulating c-reactive protein levels with central Alzheimer’s disease biomarkers. The Journal of Prevention of Alzheimer s Disease. 2025. doi:10.1016/j.tjpad.2025.100368. PMID: 40967969.
BibTeX
@article{choi2025-40967969,
author = {Choi, Hyeji and Byun, Min Soo and Yi, Dahyun and Ahn, Hyejin and Jung, Gijung and Park, Sang‐Yong and Jung, Joon Hyung and Keum, Musung and others},
title = {{Associations of circulating c-reactive protein levels with central Alzheimer’s disease biomarkers}},
journal = {The Journal of Prevention of Alzheimer s Disease},
year = {2025},
doi = {10.1016/j.tjpad.2025.100368},
pmid = {40967969},
url = {https://doi.org/10.1016/j.tjpad.2025.100368}
}
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