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Complement C1q-dependent excitatory and inhibitory synapse elimination by astrocytes and microglia in Alzheimer's disease mouse models
Dejanovic B, Wu T, Tsai MC, Graykowski D, Gandham VD, Rose CM, Bakalarski CE, Ngu H et al.. Nature aging, 2022-09-20
Topic: Brain proteins, microglia and lab models
Microglia and complement can mediate neurodegeneration in Alzheimer's disease (AD). By integrative multi-omics analysis, here we show that astrocytic and microglial proteins are increased in Tau P301S synapse fractions with age and in a C1q-dependent manner. In addition to microglia, we identified that astrocytes contribute substantially to synapse elimination in Tau P301S hippocampi.
Key findings
- By integrative multi-omics analysis, here we show that astrocytic and microglial proteins are increased in Tau P301S synapse fractions with age and in a C1q-dependent manner.
- In addition to microglia, we identified that astrocytes contribute substantially to synapse elimination in Tau P301S hippocampi.
- Notably, we found relatively more excitatory synapse marker proteins in astrocytic lysosomes, whereas microglial lysosomes contained more inhibitory synapse material.
- C1q deletion reduced astrocyte-synapse association and decreased astrocytic and microglial synapses engulfment in Tau P301S mice and rescued synapse density.
Why it matters
In Tau P301S mouse models, this study found that astrocytes and microglia eliminate synapses in a C1q-dependent manner. These are mouse findings and do not establish a treatment, cure, or prevention for Alzheimer's disease in humans.
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Study details
- Evidence strengthLow
How this study scored 57/100
Published in a leading specialty 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 | 9 / 10 | Tier 2 — leading specialty journal (Nature aging) |
| Journal's citation record | 1 / 4 | Nature Aging: journal h-index 103 (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 | 3 / 5 | 2022 — within 6 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 | 6 / 7 | Cited 338 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 56.3 citations a year over 6 year(s) since 2022 |
| Impact for its field and year | 4 / 6 | Cited 17.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 11 other studies in this library |
| Still being cited | 4 / 4 | Cited 298 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Jesse E. Hanson: h-index 32 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Broad Institute: institution h-index 2,541 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 37118504) |
| Free to read | 2 / 2 | Free to read |
| Total | 57 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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
Dejanovic, B., Wu, T., Tsai, M. C., Graykowski, D., Gandham, V. D., Rose, C. M., et al. (2022). Complement C1q-dependent excitatory and inhibitory synapse elimination by astrocytes and microglia in Alzheimer's disease mouse models. Nature aging. https://doi.org/10.1038/s43587-022-00281-1
Vancouver
Dejanovic B, Wu T, Tsai MC, Graykowski D, Gandham VD, Rose CM, et al. Complement C1q-dependent excitatory and inhibitory synapse elimination by astrocytes and microglia in Alzheimer's disease mouse models. Nature aging. 2022. doi:10.1038/s43587-022-00281-1. PMID: 37118504.
BibTeX
@article{dejanovic2022-37118504,
author = {Dejanovic, B. and Wu, T. and Tsai, M. C. and Graykowski, D. and Gandham, V. D. and Rose, C. M. and Bakalarski, C. E. and Ngu, H. and others},
title = {{Complement C1q-dependent excitatory and inhibitory synapse elimination by astrocytes and microglia in Alzheimer's disease mouse models}},
journal = {Nature aging},
year = {2022},
doi = {10.1038/s43587-022-00281-1},
pmid = {37118504},
url = {https://doi.org/10.1038/s43587-022-00281-1}
}
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