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Plasma inflammatory biomarker associations with Alzheimers disease clinical stage and CSF biomarkers: evaluation of sex effects
Coig, R.; Jain, L.; Khrestian, M.; Tuason, E.; Rao, S.; Pillai, J. A.; Leverenz, J. B.; Bekris et al.. medRxiv (preprint), 2026-08-17
Topic: Amyloid, tau and blood-test diagnosis
BackgroundAlzheimers disease (AD) is characterized by amyloid beta and tau accumulation accompanied by altered inflammatory responses. Sex is an important modifier of AD risk and pathology, however, its influence on relationships between peripheral inflammatory markers and cerebrospinal fluid (CSF) AD biomarkers remains unclear. The aim of this study was to determine whether sex modifies peripheral inflammatory biomarker relationships associated with AD pathology and clinical stage. Materials and MethodsTwelve CSF biomarkers and 41 plasma biomarkers spanning AD pathology, neurodegeneration, and inflammation were measured on the Luminex platform in a cross-sectional cohort of 261 participants from the Cleveland Clinic Lou Ruvo Center for Brain Health Biobank. Associations were evaluated in sex-adjusted, sex-interaction, and sex-stratified models, accounting for age, APOE4 carrier status, and diagnosis. ResultsPlasma IL-5 was inversely associated with clinical stage, and 10 plasma inflammatory markers, including Flt-3L, MCP-1, soluble TREM2 (sTREM2), TNF, IL-8, IL-5, IL-12P40, IL-1RA, fractalkine, and G-CSF, were inversely associated with the CSF pTau181/A{beta}42 ratio in pooled models adjusted for sex. Although formal biomarker x sex interactions did not survive FDR correction, significant associations between the CSF pTau181/A{beta}42 ratio and plasma MCP-1 and IL-12P40 were observed in females but not males. DiscussionOur findings identify a group of peripheral inflammatory markers associated with AD pathology and suggest that some of these relationships may vary by sex, warranting larger studies to clarify the role of sex in AD pathobiology.
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APA 7th
Coig, R., Jain, L., Khrestian, M., Tuason, E., Rao, S., Pillai, J. A., et al. (2026). Plasma inflammatory biomarker associations with Alzheimers disease clinical stage and CSF biomarkers: evaluation of sex effects. medRxiv (preprint). https://doi.org/10.64898/2026.08.12.26360207
Vancouver
Coig R, Jain L, Khrestian M, Tuason E, Rao S, Pillai JA, et al. Plasma inflammatory biomarker associations with Alzheimers disease clinical stage and CSF biomarkers: evaluation of sex effects. medRxiv (preprint). 2026. doi:10.64898/2026.08.12.26360207.
BibTeX
@article{coig2026-0c982ec3,
author = {Coig, R. and Jain, L. and Khrestian, M. and Tuason, E. and Rao, S. and Pillai, J. A. and Leverenz, J. B. and Bekris and others},
title = {{Plasma inflammatory biomarker associations with Alzheimers disease clinical stage and CSF biomarkers: evaluation of sex effects}},
journal = {medRxiv (preprint)},
year = {2026},
doi = {10.64898/2026.08.12.26360207},
url = {https://doi.org/10.64898/2026.08.12.26360207}
}
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.
Key findings
- The aim of this study was to determine whether sex modifies peripheral inflammatory biomarker relationships associated with AD pathology and clinical stage.
- ResultsPlasma IL-5 was inversely associated with clinical stage, and 10 plasma inflammatory markers, including Flt-3L, MCP-1, soluble TREM2 (sTREM2), TNF, IL-8, IL-5, IL-12P40, IL-1RA, fractalkine, and G-CSF, were inversely associated with the CSF pTau181/A{beta}42 ratio in pooled models adjusted fo
- Although formal biomarker x sex interactions did not survive FDR correction, significant associations between the CSF pTau181/A{beta}42 ratio and plasma MCP-1 and IL-12P40 were observed in females but not males.
- DiscussionOur findings identify a group of peripheral inflammatory markers associated with AD pathology and suggest that some of these relationships may vary by sex, warranting larger studies to clarify the role of sex in AD pathobiology.
Why it matters
Several plasma inflammatory markers were inversely associated with the CSF pTau181/Aβ42 ratio in pooled models, but formal biomarker-by-sex interactions did not survive correction. This is a cross-sectional biomarker study and does not test any treatment or prevention.
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Study details
- Study designcross-sectional
- Participants261
- Evidence strengthModerate
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 34 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for effect reported and randomised / blinded because the record does not state it. We have no data on impact for its field and year, so that was left out: it earned 32 of the 94 points we could judge it on, which is 34 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv (preprint)) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 2 / 4 | 261 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 | 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 | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| 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 | 2 / 4 | Last-listed author Lynn M. Bekris: h-index 32 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 2 / 2 | Free to read |
| Points | 32 / 94 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 32 of the 94 points we could judge it on is 34 out of 100. |
| Total | 34 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
Read the original
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