Causality relationship between 91 inflammatory factors and Alzheimer disease: A bidirectional Mendelian randomization study
李琪佳, Shunyou Jing, Ning Li, Xiaokui Yuan, Tong Wang. Medicine, 2026-04-24
Topic: Amyloid, tau and blood-test diagnosis
Alzheimer disease (AD) is a neurodegenerative disorder characterized by amyloid plaque deposition, neurofibrillary tangles, and chronic neuroinflammation. Due to its complexity and difficult-to-treat nature, it has cast a huge shadow over global health. In addition to genetic susceptibility, the development of AD is closely related to systemic inflammation. This study aims to evaluate the association between systemic inflammatory factors and AD through a bidirectional Mendelian randomization (MR) design. Our MR design incorporated aggregated data from extensive genome-wide association studies to investigate the causal relationship between genetically determined systemic inflammatory factors and AD. The MR analysis results identified 9 potential systemic inflammatory regulatory factors: C-X-C motif chemokine 5, interleukin-18 receptor 1, interleukin-6, and tumor necrosis factor, which were associated with an increased risk. Conversely, AD is significantly correlated with 5 circulating inflammatory regulatory factors, namely, tumor necrosis factor-related apoptosis-inducing ligand, stem cell factor, monocyte chemoattractant protein-4, interleukin-5, and cystatin D, which are considered downstream consequences of AD. It is worth noting that our results have, for the first time, clarified the significant roles of inflammatory factors such as cystatin D and monocyte chemoattractant protein-4 in AD, providing new markers and key targets for further exploration of the molecular mechanism and clinical diagnosis and treatment of AD.
Key findings
- The MR analysis results identified 9 potential systemic inflammatory regulatory factors: C-X-C motif chemokine 5, interleukin-18 receptor 1, interleukin-6, and tumor necrosis factor, which were associated with an increased risk.
- Conversely, AD is significantly correlated with 5 circulating inflammatory regulatory factors, namely, tumor necrosis factor-related apoptosis-inducing ligand, stem cell factor, monocyte chemoattractant protein-4, interleukin-5, and cystatin D, which are considered downstream consequences of AD.
- It is worth noting that our results have, for the first time, clarified the significant roles of inflammatory factors such as cystatin D and monocyte chemoattractant protein-4 in AD, providing new markers and key targets for further exploration of the molecular mechanism and clinical diagnosis and treatment of AD.
Why it matters
Nine systemic inflammatory factors were associated with increased Alzheimer's disease risk, while five circulating inflammatory factors were considered downstream consequences of the disease. These results clarify the roles of inflammatory factors such as cystatin D and monocyte chemoattractant protein-4.
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Study details
- Evidence strengthLow
How this study scored 32/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 31 of the 96 points we could judge it on, which is 32 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Medicine) |
| Journal's citation record | 3 / 4 | Medicine: journal h-index 285 (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 | 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 | 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 | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| 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 | OpenAlex's profile for last-listed author Tong Wang holds only 6 work(s), too few to judge a track record — left out of this score |
| Institution's track record | 0 / 3 | University of Electronic Science and Technology of China: institution h-index 530 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 42071824) |
| Free to read | 2 / 2 | Free to read |
| Points | 31 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 31 of the 96 points we could judge it on is 32 out of 100. |
| Total | 32 / 100 | — |
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APA 7th
李琪佳, Jing, S., Li, N., Yuan, X., & Wang, T. (2026). Causality relationship between 91 inflammatory factors and Alzheimer disease: A bidirectional Mendelian randomization study. Medicine. https://doi.org/10.1097/md.0000000000048136
Vancouver
李琪佳, Jing S, Li N, Yuan X, Wang T. Causality relationship between 91 inflammatory factors and Alzheimer disease: A bidirectional Mendelian randomization study. Medicine. 2026. doi:10.1097/md.0000000000048136. PMID: 42071824.
BibTeX
@article{study2026-42071824,
author = {李琪佳 and Jing, Shunyou and Li, Ning and Yuan, Xiaokui and Wang, Tong},
title = {{Causality relationship between 91 inflammatory factors and Alzheimer disease: A bidirectional Mendelian randomization study}},
journal = {Medicine},
year = {2026},
doi = {10.1097/md.0000000000048136},
pmid = {42071824},
url = {https://doi.org/10.1097/md.0000000000048136}
}
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