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Complement and microglia mediate early synapse loss in Alzheimer mouse models
Hong S, Beja-Glasser VF, Nfonoyim BM, Frouin A, Li S, Ramakrishnan S, Merry KM, Shi Q et al.. Science (New York, N.Y.), 2016-03-31
Topic: Brain proteins, microglia and lab models
Synapse loss in Alzheimer's disease (AD) correlates with cognitive decline. Involvement of microglia and complement in AD has been attributed to neuroinflammation, prominent late in disease. Here we show in mouse models that complement and microglia mediate synaptic loss early in AD.
Key findings
- Involvement of microglia and complement in AD has been attributed to neuroinflammation, prominent late in disease.
- Here we show in mouse models that complement and microglia mediate synaptic loss early in AD.
- C1q, the initiating protein of the classical complement cascade, is increased and associated with synapses before overt plaque deposition.
- Inhibition of C1q, C3, or the microglial complement receptor CR3 reduces the number of phagocytic microglia, as well as the extent of early synapse loss.
Why it matters
In mouse models of Alzheimer's, this study reports that the complement protein C1q was increased and associated with synapses before overt plaque deposition. Blocking C1q, C3 or the microglial receptor CR3 reduced both the number of phagocytic microglia and the extent of early synapse loss. The authors argue that complement and microglia act early in the disease, not only through late-stage inflammation. These are mouse results with no human data and no reported memory outcomes, so they point to a research target, not a treatment.
Study details
- Evidence strengthLow
How this study scored 64/100
Published in a top-tier journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (Science (New York, N.Y.)) |
| Journal's citation record | 4 / 4 | Science: journal h-index 1,754 (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 | 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 | Laboratory or animal study (title names “mouse”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 7 / 7 | Cited 3,317 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 276.4 citations a year over 12 year(s) since 2016 |
| Impact for its field and year | 6 / 6 | Cited 114.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 5 / 6 | Cited by 114 other studies in this library |
| Still being cited | 4 / 4 | Cited 1,156 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Beth A. Stevens: h-index 78 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 12 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 27033548) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 64 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Hong, S., Beja-Glasser, V. F., Nfonoyim, B. M., Frouin, A., Li, S., Ramakrishnan, S., et al. (2016). Complement and microglia mediate early synapse loss in Alzheimer mouse models. Science (New York, N.Y.). https://doi.org/10.1126/science.aad8373
Vancouver
Hong S, Beja-Glasser VF, Nfonoyim BM, Frouin A, Li S, Ramakrishnan S, et al. Complement and microglia mediate early synapse loss in Alzheimer mouse models. Science (New York, N.Y.). 2016. doi:10.1126/science.aad8373. PMID: 27033548.
BibTeX
@article{hong2016-27033548,
author = {Hong, S. and Beja-Glasser, V. F. and Nfonoyim, B. M. and Frouin, A. and Li, S. and Ramakrishnan, S. and Merry, K. M. and Shi, Q. and others},
title = {{Complement and microglia mediate early synapse loss in Alzheimer mouse models}},
journal = {Science (New York, N.Y.)},
year = {2016},
doi = {10.1126/science.aad8373},
pmid = {27033548},
url = {https://doi.org/10.1126/science.aad8373}
}
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