Assessing the causal association between celiac disease and Alzheimer disease and frontotemporal dementia: A bidirectional Mendelian randomization approach
Yu Liu, Hongmei Zhang. Medicine, 2025-10-17
Topic: Amyloid, tau and blood-test diagnosis
This study aimed to investigate the bidirectional causal relationship between celiac disease (CD) and the risk of Alzheimer disease (AD) or frontotemporal dementia (FTD) using Mendelian randomization (MR), in order to clarify prior inconsistent findings. We analyzed summary-level genome-wide association study (GWAS) data for CD, AD, and FTD. Single-nucleotide polymorphisms (SNPs) strongly associated with each condition were selected as genetic instruments. MR analysis was conducted in 2 directions: from CD to AD/FTD and from AD/FTD to CD. Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) was used to detect and correct for pleiotropy, and Cochran Q assessed heterogeneity. Leave-one-out and Mendelian Randomization-Egger (MR-Egger) regression sensitivity analyses were performed to evaluate robustness. No evidence of a causal effect was found between CD and either AD or FTD in either direction (P > .05). Similarly, genetic liability to AD or FTD did not increase the risk of CD. Sensitivity analyses supported the robustness of the results, showing no pleiotropy or heterogeneity. Our findings suggest that CD is not causally linked to the development of AD or FTD. While shared genetic factors or comorbidities may exist, the association is likely noncausal, and other mechanisms of cognitive decline in CD patients warrant further study.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Liu, Y., & Zhang, H. (2025). Assessing the causal association between celiac disease and Alzheimer disease and frontotemporal dementia: A bidirectional Mendelian randomization approach. Medicine. https://doi.org/10.1097/md.0000000000045059
Vancouver
Liu Y, Zhang H. Assessing the causal association between celiac disease and Alzheimer disease and frontotemporal dementia: A bidirectional Mendelian randomization approach. Medicine. 2025. doi:10.1097/md.0000000000045059. PMID: 41189247.
BibTeX
@article{liu2025-41189247,
author = {Liu, Yu and Zhang, Hongmei},
title = {{Assessing the causal association between celiac disease and Alzheimer disease and frontotemporal dementia: A bidirectional Mendelian randomization approach}},
journal = {Medicine},
year = {2025},
doi = {10.1097/md.0000000000045059},
pmid = {41189247},
url = {https://doi.org/10.1097/md.0000000000045059}
}
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Key findings
- Single-nucleotide polymorphisms (SNPs) strongly associated with each condition were selected as genetic instruments.
- Sensitivity analyses supported the robustness of the results, showing no pleiotropy or heterogeneity.
- Our findings suggest that CD is not causally linked to the development of AD or FTD.
Why it matters
This Mendelian randomization study found no evidence of a causal effect between celiac disease and either Alzheimer disease or frontotemporal dementia in either direction. The authors conclude the association is likely noncausal, and no treatment, cure, or prevention is reported.
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Study details
- Evidence strengthLow
How this study scored 34/100
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 33 of the 96 points we could judge it on, which is 34 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 | 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 | 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 | 1 / 7 | Cited 1 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 1 / 6 | Cited 0.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 0 / 4 | Cited 1 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 0 / 3 | Capital Medical University: institution h-index 643 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41189247) |
| Free to read | 2 / 2 | Free to read |
| Points | 33 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 33 of the 96 points we could judge it on is 34 out of 100. |
| Total | 34 / 100 | — |
What each of these 20 components measures, and what this score is not →
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