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Trajectory of plasma lipidome associated with the risk of late-onset Alzheimer's disease: a longitudinal cohort study
Tingting Wang, Matthias Arnold, Kevin Huynh, Patrick Weinisch, Corey Giles, Natalie A. Mellett, Thy Duong, Bharadwaj Marella et al.. EBioMedicine, 2025-07-01
Topic: Amyloid, tau and blood-test diagnosis
Background Comprehensive lipidomic studies have demonstrated strong cross-sectional associations between the blood lipidome and late-onset Alzheimer's disease (AD) dementia and its risk factors, yet the longitudinal relationship between lipidome changes and AD progression remains unclear. Findings Longitudinal analysis identified significant associations between the change in ether lipid species (including alkylphosphatidylcholine, alkenylphosphatidylcholine, lysoalkylphosphatidylcholine, and lysoalkenylphosphatidylcholine) and AD dementia conversion. Specifically, AD dementia converters show a 3–4.8% reduction in these ether lipid species compared to the non-converting CN and MCI groups, suggesting metabolic dysregulation as a key feature of AD progression. Within the MCI group, the model identified a high-risk subgroup with a twofold higher likelihood of conversion to AD dementia compared to the low-risk group. Additionally, the Dementia Risk Score was significantly associated with reduced temporal lobar fludeoxyglucose uptake (β = −0.286, p=1.34 × 10 −4 ), higher amyloid PET levels (β = 0.308, p=4.03 × 10 −4 ), and elevated p-tau levels (β = 0.167, p=2.37 × 10 −2 ), reinforcing its pathophysiological relevance in tracking neurodegeneration, amyloid burden, and tau pathology. Interpretation These findings highlight lipidomic profiling as a potential blood-based biomarker for identifying individuals at high risk of AD progression, offering a scalable, non-invasive approach for early detection, risk stratification, and targeted interventions in AD.
Key findings
- Background Comprehensive lipidomic studies have demonstrated strong cross-sectional associations between the blood lipidome and late-onset Alzheimer's disease (AD) dementia and its risk factors, yet the longitudinal relationship between lipidome changes and AD progression remains unclear.
- Findings Longitudinal analysis identified significant associations between the change in ether lipid species (including alkylphosphatidylcholine, alkenylphosphatidylcholine, lysoalkylphosphatidylcholine, and lysoalkenylphosphatidylcholine) and AD dementia conversion.
- Specifically, AD dementia converters show a 3–4.8% reduction in these ether lipid species compared to the non-converting CN and MCI groups, suggesting metabolic dysregulation as a key feature of AD progression.
- Within the MCI group, the model identified a high-risk subgroup with a twofold higher likelihood of conversion to AD dementia compared to the low-risk group.
- Additionally, the Dementia Risk Score was significantly associated with reduced temporal lobar fludeoxyglucose uptake (β = −0.286, p=1.34 × 10 −4 ), higher amyloid PET levels (β = 0.308, p=4.03 × 10 −4 ), and elevated p-tau levels (β = 0.167, p=2.37 × 10 −2 ), reinforcing its pathophysiological relevance in tracking neurodegeneration, amyloid burden, and tau pathology.
Why it matters
This longitudinal study found that people who developed Alzheimer's dementia showed a 3 to 4.8% drop in certain ether lipid species in blood compared with those who did not convert. The authors present lipid profiling as a potential blood-based biomarker, which could help track progression but is not itself a treatment or cure.
Study details
- Study designcross-sectional
- Participants1,393
- Effect size4.8%; AUC = 0.70
- Evidence strengthModerate
How this study scored 61/100
Published in a peer-reviewed journal, and it is a snapshot of people at one point in time. Scored zero for randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (EBioMedicine) |
| Journal's citation record | 2 / 4 | EBioMedicine: journal h-index 181 (OpenAlex, 2026-10-29) |
| 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 | 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 | 3 / 4 | 1,393 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| 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 | 2 / 7 | Cited 13 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 4 / 6 | Cited 8.3× 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 | 1 / 4 | Cited 13 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Rima F Kaddurah-Daouk: h-index 74 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Duke University: institution h-index 1,541 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 11 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40592256) |
| Free to read | 2 / 2 | Free to read |
| Total | 61 / 100 | — |
What each of these 20 components measures, and what this score is not →
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
Wang, T., Arnold, M., Huynh, K., Weinisch, P., Giles, C., Mellett, N. A., et al. (2025). Trajectory of plasma lipidome associated with the risk of late-onset Alzheimer's disease: a longitudinal cohort study. EBioMedicine. https://doi.org/10.1016/j.ebiom.2025.105826
Vancouver
Wang T, Arnold M, Huynh K, Weinisch P, Giles C, Mellett NA, et al. Trajectory of plasma lipidome associated with the risk of late-onset Alzheimer's disease: a longitudinal cohort study. EBioMedicine. 2025. doi:10.1016/j.ebiom.2025.105826. PMID: 40592256.
BibTeX
@article{wang2025-40592256,
author = {Wang, Tingting and Arnold, Matthias and Huynh, Kevin and Weinisch, Patrick and Giles, Corey and Mellett, Natalie A. and Duong, Thy and Marella, Bharadwaj and others},
title = {{Trajectory of plasma lipidome associated with the risk of late-onset Alzheimer's disease: a longitudinal cohort study}},
journal = {EBioMedicine},
year = {2025},
doi = {10.1016/j.ebiom.2025.105826},
pmid = {40592256},
url = {https://doi.org/10.1016/j.ebiom.2025.105826}
}
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