Apolipoprotein E lipoprotein particles inhibit amyloid-β uptake through cell surface heparan sulphate proteoglycan
Yuan Fu, Jing Zhao, Yuka Atagi, Henrietta M Nielsen, Chia-Chen Liu, Honghua Zheng, Mitsuru Shinohara, Takahisa Kanekiyo et al.. Molecular neurodegeneration, 2016-05-05
Topic: Disease mechanisms in lab and animal studies
In this study, we show that apoE lipoprotein particles from conditioned media of immortalized astrocytes isolated from human APOE-targeted replacement (TR) mice significantly suppress cellular Aβ42 and Aβ40 uptake through cell surface HSPG. ApoE3 and apoE4 particles have similar binding affinity to heparin, while apoE4 particles are likely hypolipidated compared to apoE particles. We also found that the apoE particles antagonize Aβ binding to cell surface, and inhibited Aβ uptake in a concentration-dependent manner in Chinese hamster ovary (CHO) cells. While the effect was not apoE isoform-dependent, the suppressive effect of apoE particles on Aβ uptake was not observed in HSPG-deficient CHO cells. We further demonstrated that apoE particles reduced the internalization of Aβ in mouse primary neurons, an effect that is eliminated by the presence of heparin. Taken together, our findings indicate that apoE particles irrespective of isoform inhibit HSPG-dependent cellular Aβ uptake. Modulating the ability of apoE particles to affect Aβ cellular uptake may hold promises for developing new strategies for AD therapy.
Key findings
- In this study, we show that apoE lipoprotein particles from conditioned media of immortalized astrocytes isolated from human APOE-targeted replacement (TR) mice significantly suppress cellular Aβ42 and Aβ40 uptake through cell surface HSPG.
- ApoE3 and apoE4 particles have similar binding affinity to heparin, while apoE4 particles are likely hypolipidated compared to apoE particles.
- We also found that the apoE particles antagonize Aβ binding to cell surface, and inhibited Aβ uptake in a concentration-dependent manner in Chinese hamster ovary (CHO) cells.
- While the effect was not apoE isoform-dependent, the suppressive effect of apoE particles on Aβ uptake was not observed in HSPG-deficient CHO cells.
- We further demonstrated that apoE particles reduced the internalization of Aβ in mouse primary neurons, an effect that is eliminated by the presence of heparin.
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Study details
- Evidence strengthLow
How this study scored 38/100
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 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, multi-centre collaboration and free to read, so those were left out: it earned 21 of the 56 points we could judge it on, which is 38 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Molecular neurodegeneration) |
| 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 | 1 / 5 | 2016 — within 20 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 27151330) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 21 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 21 of the 56 points we could judge it on is 38 out of 100. |
| Total | 38 / 100 | — |
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APA 7th
Fu, Y., Zhao, J., Atagi, Y., Nielsen, H. M., Liu, C.-C., Zheng, H., et al. (2016). Apolipoprotein E lipoprotein particles inhibit amyloid-β uptake through cell surface heparan sulphate proteoglycan. Molecular neurodegeneration. https://doi.org/10.1186/s13024-016-0099-y
Vancouver
Fu Y, Zhao J, Atagi Y, Nielsen HM, Liu C.-C, Zheng H, et al. Apolipoprotein E lipoprotein particles inhibit amyloid-β uptake through cell surface heparan sulphate proteoglycan. Molecular neurodegeneration. 2016. doi:10.1186/s13024-016-0099-y. PMID: 27151330.
BibTeX
@article{fu2016-27151330,
author = {Fu, Yuan and Zhao, Jing and Atagi, Yuka and Nielsen, Henrietta M and Liu, Chia-Chen and Zheng, Honghua and Shinohara, Mitsuru and Kanekiyo, Takahisa and others},
title = {{Apolipoprotein E lipoprotein particles inhibit amyloid-β uptake through cell surface heparan sulphate proteoglycan}},
journal = {Molecular neurodegeneration},
year = {2016},
doi = {10.1186/s13024-016-0099-y},
pmid = {27151330},
url = {https://doi.org/10.1186/s13024-016-0099-y}
}