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Lysophosphatidylcholines are associated with amyloidosis in early stages of Alzheimer's disease
Kalia V, Reyes-Dumeyer D, Dubey S, Udhani H, Nandakumar R, Lee AJ, Lantigua R, Medrano M et al.. Nature aging, 2025-12-17
Topic: Brain proteins, microglia and lab models
Circulating metabolites can identify biochemical risk factors related to Alzheimer's disease (AD). We measured plasma metabolites in 1,068 participants of Caribbean Hispanic ancestry (250 patients with AD and 818 healthy controls) across 2 cohorts and analyzed their relationship with clinical AD, biomarker-supported AD and plasma biomarkers (P-tau181, P-tau217, P-tau231 and Aβ42:Aβ40). Amino acid metabolism pathways were enriched among metabolites associated with P-tau biomarkers, whereas sialic acid and N-glycan pathways were associated with Aβ42:Aβ40. Through several dimensionality reduction approaches, we identified an APOE-ε4 dependent relationship between lysophosphatidylcholines (lysoPCs) carrying polyunsaturated fatty acids and biomarker-supported AD and P-tau biomarkers. In an independent dataset of 110 postmortem brain tissues from non-Hispanic white participants, lysoPCs in the brain were also associated with AD neuropathological features. Our results show that biomarker-based diagnostic criteria identified an APOE-ε4 dependent association with lysoPCs, which play a critical role in the transport of neuroprotective polyunsaturated fatty acids into the brain, and AD.
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APA 7th
Kalia, V., Reyes-Dumeyer, D., Dubey, S., Udhani, H., Nandakumar, R., Lee, A. J., et al. (2026). Lysophosphatidylcholines are associated with amyloidosis in early stages of Alzheimer's disease. Nature aging. https://doi.org/10.1038/s43587-025-01025-7
Vancouver
Kalia V, Reyes-Dumeyer D, Dubey S, Udhani H, Nandakumar R, Lee AJ, et al. Lysophosphatidylcholines are associated with amyloidosis in early stages of Alzheimer's disease. Nature aging. 2026. doi:10.1038/s43587-025-01025-7. PMID: 41407938.
BibTeX
@article{kalia2026-41407938,
author = {Kalia, V. and Reyes-Dumeyer, D. and Dubey, S. and Udhani, H. and Nandakumar, R. and Lee, A. J. and Lantigua, R. and Medrano, M. and others},
title = {{Lysophosphatidylcholines are associated with amyloidosis in early stages of Alzheimer's disease}},
journal = {Nature aging},
year = {2026},
doi = {10.1038/s43587-025-01025-7},
pmid = {41407938},
url = {https://doi.org/10.1038/s43587-025-01025-7}
}
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Key findings
- Amino acid metabolism pathways were enriched among metabolites associated with P-tau biomarkers, whereas sialic acid and N-glycan pathways were associated with Aβ42:Aβ40.
- In an independent dataset of 110 postmortem brain tissues from non-Hispanic white participants, lysoPCs in the brain were also associated with AD neuropathological features.
- Our results show that biomarker-based diagnostic criteria identified an APOE-ε4 dependent association with lysoPCs, which play a critical role in the transport of neuroprotective polyunsaturated fatty acids into the brain, and AD.
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Study details
- Participants1,068
- Evidence strengthLow
How this study scored 60/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomized / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 35 of the 58 points we could judge it on, which is 60 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature aging) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 3 / 4 | 1,068 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| 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 | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41407938) |
| Free to read | 2 / 2 | Free to read |
| Points | 35 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 35 of the 58 points we could judge it on is 60 out of 100. |
| Total | 60 / 100 | — |
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