Apolipoprotein E promotes astrocyte colocalization and degradation of deposited amyloid-beta peptides
Koistinaho M, Lin S, Wu X, Esterman M, Koger D, Hanson J, Higgs R, Liu F et al.. Nature medicine, 2004-06-13
Topic: Brain proteins, microglia and lab models
We have previously shown that apolipoprotein E (Apoe) promotes the formation of amyloid in brain and that astrocyte-specific expression of APOE markedly affects the deposition of amyloid-beta peptides (Abeta) in a mouse model of Alzheimer disease. Given the capacity of astrocytes to degrade Abeta, we investigated the potential role of Apoe in this astrocyte-mediated degradation. In contrast to cultured adult wild-type mouse astrocytes, adult Apoe(-/-) astrocytes do not degrade Abeta present in Abeta plaque-bearing brain sections in vitro. Coincubation with antibodies to either Apoe or Abeta, or with RAP, an antagonist of the low-density lipoprotein receptor family, effectively blocks Abeta degradation by astrocytes. Phase-contrast and confocal microscopy show that Apoe(-/-) astrocytes do not respond to or internalize Abeta deposits to the same extent as do wild-type astrocytes. Thus, Apoe seems to be important in the degradation and clearance of deposited Abeta species by astrocytes, a process that may be impaired in Alzheimer disease.
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APA 7th
Koistinaho, M., Lin, S., Wu, X., Esterman, M., Koger, D., Hanson, J., et al. (2004). Apolipoprotein E promotes astrocyte colocalization and degradation of deposited amyloid-beta peptides. Nature medicine. https://doi.org/10.1038/nm1058
Vancouver
Koistinaho M, Lin S, Wu X, Esterman M, Koger D, Hanson J, et al. Apolipoprotein E promotes astrocyte colocalization and degradation of deposited amyloid-beta peptides. Nature medicine. 2004. doi:10.1038/nm1058. PMID: 15195085.
BibTeX
@article{koistinaho2004-15195085,
author = {Koistinaho, M. and Lin, S. and Wu, X. and Esterman, M. and Koger, D. and Hanson, J. and Higgs, R. and Liu, F. and others},
title = {{Apolipoprotein E promotes astrocyte colocalization and degradation of deposited amyloid-beta peptides}},
journal = {Nature medicine},
year = {2004},
doi = {10.1038/nm1058},
pmid = {15195085},
url = {https://doi.org/10.1038/nm1058}
}
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Key findings
- We have previously shown that apolipoprotein E (Apoe) promotes the formation of amyloid in brain and that astrocyte-specific expression of APOE markedly affects the deposition of amyloid-beta peptides (Abeta) in a mouse model of Alzheimer disease.
Why it matters
In dishes of brain tissue containing amyloid plaques, astrocytes (brain support cells) from normal mice broke down the deposited amyloid-beta, but astrocytes from mice lacking apolipoprotein E did not, and they took up less of the deposits. Blocking apoE, amyloid-beta, or the LDL-receptor family of receptors also stopped the breakdown, so the authors conclude apoE "seems to be important" for astrocytes to clear deposited amyloid, a process they suggest "may be impaired in Alzheimer disease." This was a laboratory mouse-cell study with no reported effect sizes; it did not test APOE variants, people, or any treatment.
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Study details
- Evidence strengthLow
How this study scored 52/100
Published in a top-tier journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (Nature medicine) |
| Journal's citation record | 4 / 4 | Nature Medicine: journal h-index 763 (OpenAlex, 2026-10-29) |
| 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 | 2004 — older than 20 years, still counted |
| 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 | 6 / 7 | Cited 569 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 23.7 citations a year over 24 year(s) since 2004 |
| Impact for its field and year | 4 / 6 | Cited 12.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 37 other studies in this library |
| Still being cited | 2 / 4 | Cited 48 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Steven M. Paul: h-index 81 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Eli Lilly (United States): institution h-index 744 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 15195085) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 52 / 100 | — |
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