APOE genotypes differentially remodel the astrocytic lipid droplet-associated proteome to shape lipid droplet dynamics
Carla Cuní-López, Jessica T Root, Ying Hao, Isabelle Kowal, Niek Blomberg, Rodolfo Ghirlando, Linda G Yang, Sascha J Koppes-den Hertog et al.. bioRxiv : the preprint server for biology, 2025-08-20
Topic: Genetics and APOE
The lipids and proteins that comprise lipid droplets regulate several cellular functions including lipid storage, stress responses, and inflammation. Glial lipid droplets have been implicated in the pathogenesis and progression of Alzheimer's disease (AD), yet the mechanisms linking genetic risk to lipid droplet biology remain unclear. Here we examined how APOE, the strongest genetic modulator of late-onset AD, impacts lipid droplet composition and dynamics. We defined the lipid droplet-associated proteome and lipidome in human induced pluripotent stem cell-derived astrocytes harboring the three common APOE genotypes: APOE2 (protective), APOE3 (neutral), and APOE4 (risk). Each APOE variant displays distinct lipid droplet-associated proteins and lipids. These molecular changes yield differences in lipophagy; lipid droplets in APOE2 astrocytes undergo autophagic turnover, whereas those in APOE4 astrocytes are resistant to degradation. These findings suggest that impaired lipid droplet clearance, rather than accumulation, distinguishes APOE4-associated AD risk, and may present a new metabolic node for modulating risk.
Key findings
- These findings suggest that impaired lipid droplet clearance, rather than accumulation, distinguishes APOE4-associated AD risk, and may present a new metabolic node for modulating risk.
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Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 22 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. 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 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, multi-centre collaboration and free to read, so those were left out: it earned 13 of the 60 points we could judge it on, which is 22 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (bioRxiv : the preprint server for biology) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| 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 | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| 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 | — / 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 |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40894647) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 13 / 60 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 13 of the 60 points we could judge it on is 22 out of 100. |
| Total | 22 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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APA 7th
Cuní-López, C., Root, J. T., Hao, Y., Kowal, I., Blomberg, N., Ghirlando, R., et al. (2025). APOE genotypes differentially remodel the astrocytic lipid droplet-associated proteome to shape lipid droplet dynamics. bioRxiv : the preprint server for biology. https://doi.org/10.1101/2025.08.19.669163
Vancouver
Cuní-López C, Root JT, Hao Y, Kowal I, Blomberg N, Ghirlando R, et al. APOE genotypes differentially remodel the astrocytic lipid droplet-associated proteome to shape lipid droplet dynamics. bioRxiv : the preprint server for biology. 2025. doi:10.1101/2025.08.19.669163. PMID: 40894647.
BibTeX
@article{cunilopez2025-40894647,
author = {Cuní-López, Carla and Root, Jessica T and Hao, Ying and Kowal, Isabelle and Blomberg, Niek and Ghirlando, Rodolfo and Yang, Linda G and Hertog, Sascha J Koppes-den and others},
title = {{APOE genotypes differentially remodel the astrocytic lipid droplet-associated proteome to shape lipid droplet dynamics}},
journal = {bioRxiv : the preprint server for biology},
year = {2025},
doi = {10.1101/2025.08.19.669163},
pmid = {40894647},
url = {https://doi.org/10.1101/2025.08.19.669163}
}