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Microglial activation by Alzheimer amyloid precursor protein and modulation by apolipoprotein E
Barger SW, Harmon AD.. Nature, 1997-08-01
Topic: Amyloid, tau and blood-test diagnosis
A role for beta-amyloid precursor protein (beta-APP) in the development of Alzheimer's disease has been indicated by genetics, and many conditions in which beta-APP is raised have been associated with an increased risk of Alzheimer's disease or an Alzheimer's-like pathology. Inflammatory events may also contribute to Alzheimer's disease. Here we investigate whether a secreted derivative of beta-APP (sAPP-alpha) can induce inflammatory reactions in microglia, which are brain cells of monocytic lineage.
Key findings
- Inflammatory events may also contribute to Alzheimer's disease.
- Here we investigate whether a secreted derivative of beta-APP (sAPP-alpha) can induce inflammatory reactions in microglia, which are brain cells of monocytic lineage.
- We found that treatment with sAPP-alpha increased markers of activation in microglia and enhanced their production of neurotoxins.
- The ability of sAPP-alpha to activate microglia was blocked by prior incubation of the protein with apolipoprotein E3 but not apolipoprotein E4, a variant associated with an increased risk for Alzheimer's.
Why it matters
In laboratory experiments, a secreted fragment of APP activated microglia and increased their production of neurotoxins, and this was blocked by apolipoprotein E3 but not E4. This suggests a possible link between APP, inflammation, and apolipoprotein E, but it is early laboratory work and no treatment was tested.
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Study details
- Evidence strengthLow
How this study scored 50/100
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. We have no data on senior author's track record, so that was left out: it earned 48 of the 96 points we could judge it on, which is 50 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (Nature) |
| Journal's citation record | 4 / 4 | Nature: journal h-index 1,841 (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 | 1997 — 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 624 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 20.1 citations a year over 31 year(s) since 1997 |
| Impact for its field and year | 4 / 6 | Cited 18.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 29 other studies in this library |
| Still being cited | 2 / 4 | Cited 32 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | OpenAlex's profile for last-listed author Ashley Harmon holds only 3 work(s), too few to judge a track record — left out of this score |
| Institution's track record | 0 / 3 | University of Arkansas for Medical Sciences: institution h-index 591 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 9278049) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 48 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 48 of the 96 points we could judge it on is 50 out of 100. |
| Total | 50 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Barger, S. W., & Harmon, A. D. (1997). Microglial activation by Alzheimer amyloid precursor protein and modulation by apolipoprotein E. Nature. https://doi.org/10.1038/42257
Vancouver
Barger SW, Harmon AD. Microglial activation by Alzheimer amyloid precursor protein and modulation by apolipoprotein E. Nature. 1997. doi:10.1038/42257. PMID: 9278049.
BibTeX
@article{barger1997-9278049,
author = {Barger, S. W. and Harmon, A. D.},
title = {{Microglial activation by Alzheimer amyloid precursor protein and modulation by apolipoprotein E}},
journal = {Nature},
year = {1997},
doi = {10.1038/42257},
pmid = {9278049},
url = {https://doi.org/10.1038/42257}
}
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