Topic: Brain proteins, microglia and lab models
Plain-language summary
Lipidomics research could provide insights of pathobiological mechanisms in Alzheimer's disease. This study explores a battery of plasma lipids that can differentiate Alzheimer's disease (AD) patients from healthy controls and determines whether lipid profiles correlate with genetic risk for AD. AD plasma samples were collected from the Sydney Memory and Ageing Study (MAS) Sydney, Australia (aged range 75-97 years; 51.2% male). Untargeted lipidomics analysis was performed by liquid chromatography coupled-mass spectrometry (LC-MS/MS). We found that several lipid species from nine lipid classes, particularly sphingomyelins (SMs), cholesterol esters (ChEs), phosphatidylcholines (PCs), phosphatidylethanolamines (PIs), phosphatidylinositols (PIs), and triglycerides (TGs) are dysregulated in AD patients and may help discriminate them from healthy controls. However, when the lipid species were grouped together into lipid subgroups, only the DG group was significantly higher in AD. ChEs, SMs, and TGs resulted in good classification accuracy using the Glmnet algorithm (elastic net penalization for the generalized linear model [glm]) with more than 80% AUC. In general, group lipids and the lipid subclasses LPC and PE had less classification accuracy compared to the other subclasses. We also found significant increases in SMs, PIs, and the LPE/PE ratio in human U251 astroglioma cell lines exposed to pathophysiological concentrations of oligomeric Aβ 42 . This suggests that oligomeric Aβ 42 plays a contributory, if not causal role, in mediating changes in lipid profiles in AD that can be detected in the periphery. In addition, we evaluated the association of plasma lipid profiles with AD-related single nucleotide polymorphisms (SNPs) and polygenic risk scores (PRS) of AD. We found that FERMT2 and MS4A6A showed a significantly differential association with lipids in all lipid classes across disease and control groups. ABCA7 had a differential association with more than half of the DG lipids (52.63%) and PI lipids (57.14%), respectively. Additionally, 43.4% of lipids in the SM class were differentially associated with CLU. More than 30% of lipids in ChE, PE, and TG classes had differential associations with separate genes (ChE-PICALM, SLC24A4, and SORL1; PE-CLU and CR1; TG-BINI) between AD and control group. These data may provide renewed insights into the pathobiology of AD and the feasibility of identifying individuals with greater AD risk.
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APA 7th
Liu, Y., Thalamuthu, A., Mather, K. A., Crawford, J., Ulanova, M., Wong, M. W. K., et al. (2021). Plasma lipidome is dysregulated in Alzheimer's disease and is associated with disease risk genes. Translational psychiatry. https://doi.org/10.1038/s41398-021-01362-2
Vancouver
Liu Y, Thalamuthu A, Mather KA, Crawford J, Ulanova M, Wong MWK, et al. Plasma lipidome is dysregulated in Alzheimer's disease and is associated with disease risk genes. Translational psychiatry. 2021. doi:10.1038/s41398-021-01362-2. PMID: 34092785.
BibTeX
@article{liu2021-34092785,
author = {Liu, Y. and Thalamuthu, A. and Mather, K. A. and Crawford, J. and Ulanova, M. and Wong, M. W. K. and Pickford, R. and Sachdev, P. S. and others},
title = {{Plasma lipidome is dysregulated in Alzheimer's disease and is associated with disease risk genes}},
journal = {Translational psychiatry},
year = {2021},
doi = {10.1038/s41398-021-01362-2},
pmid = {34092785},
url = {https://doi.org/10.1038/s41398-021-01362-2}
}
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Key findings
- We found that several lipid species from nine lipid classes, particularly sphingomyelins (SMs), cholesterol esters (ChEs), phosphatidylcholines (PCs), phosphatidylethanolamines (PIs), phosphatidylinositols (PIs), and triglycerides (TGs) are dysregulated in AD patients and may help discriminate them from healthy controls.
- However, when the lipid species were grouped together into lipid subgroups, only the DG group was significantly higher in AD.
- In general, group lipids and the lipid subclasses LPC and PE had less classification accuracy compared to the other subclasses.
- We also found significant increases in SMs, PIs, and the LPE/PE ratio in human U251 astroglioma cell lines exposed to pathophysiological concentrations of oligomeric Aβ 42 .
- This suggests that oligomeric Aβ 42 plays a contributory, if not causal role, in mediating changes in lipid profiles in AD that can be detected in the periphery.
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Study details
- Effect size51.2%; 52.63%; 57.14%
- Evidence strengthLow
How this study scored 47/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, studied in people 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 27 of the 58 points we could judge it on, which is 47 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Translational psychiatry) |
| 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 | 3 / 5 | 2021 — within 6 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 | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| 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 34092785) |
| Free to read | 2 / 2 | Free to read |
| Points | 27 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 27 of the 58 points we could judge it on is 47 out of 100. |
| Total | 47 / 100 | — |
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