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Age‐Related Complement C3 Drives Memory Impairments and Associated Neuropathologies in a Mouse Model
Miaomiao Du, Yujia Wang, Xinyuan Wang, Yifei Liu, Fuchuan Xiao, Jing Zhang, Xia Meng, Kunhe Ma et al.. Aging Cell, 2025-06-20
Topic: Brain proteins, microglia and lab models
Aging is the greatest risk factor for learning and memory disorders; dementia prevalence significantly increases with age due to numerous molecular changes in the body. Although research has consistently shown that aging leads to learning and memory impairments, the molecular mechanisms linking aging to these cognitive deficits remain incompletely understood. Previous studies have revealed that complement C3 levels increase with age in humans, monkeys, and mice; elevated C3 expression is also observed in the brains of dementia patients. These data suggest that C3 plays critical roles in initiating learning and memory impairments. To investigate whether C3 contributes to these deficits during aging, we developed a transgenic mouse model with elevated C3 expression to simulate age-related increases. Mice with increased C3 expression showed impaired learning and memory, along with synaptic loss, neuronal loss, and astrocytosis. Quantitative polymerase chain reaction microarray and cellular assays revealed that C3 elevation may impair cognitive functions by affecting insulin signaling pathways. Notably, antibody therapy targeting complement C3 in SAMP8 mice, which naturally exhibit increased brain C3 levels, alleviated their learning and memory deficits. These findings suggest that age-related complement C3 elevation drives memory impairments and associated neuropathologies; targeting complement C3 may alleviate these deficits.
Key findings
- Aging is the greatest risk factor for learning and memory disorders; dementia prevalence significantly increases with age due to numerous molecular changes in the body.
- Although research has consistently shown that aging leads to learning and memory impairments, the molecular mechanisms linking aging to these cognitive deficits remain incompletely understood.
- Previous studies have revealed that complement C3 levels increase with age in humans, monkeys, and mice; elevated C3 expression is also observed in the brains of dementia patients.
- These data suggest that C3 plays critical roles in initiating learning and memory impairments.
- Quantitative polymerase chain reaction microarray and cellular assays revealed that C3 elevation may impair cognitive functions by affecting insulin signaling pathways.
Why it matters
In a transgenic mouse model, raising complement C3 caused learning and memory impairment with synaptic and neuronal loss, and antibody therapy targeting C3 in SAMP8 mice alleviated their memory deficits. These are animal results, and the authors suggest targeting C3 as a possible approach rather than a proven treatment.
Study details
- Evidence strengthLow
How this study scored 36/100
Published in a peer-reviewed 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 | 7 / 10 | Tier 3 — peer-reviewed journal (Aging Cell) |
| Journal's citation record | 2 / 4 | Aging Cell: journal h-index 216 (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 | 4 / 5 | 2025 — within 3 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 | 2 / 7 | Cited 6 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 1.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 6 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Jing Lu: h-index 10 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Capital Medical University: institution h-index 643 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40539508) |
| Free to read | 2 / 2 | Free to read |
| Total | 36 / 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. 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
Du, M., Wang, Y., Wang, X., Liu, Y., Xiao, F., Zhang, J., et al. (2025). Age‐Related Complement C3 Drives Memory Impairments and Associated Neuropathologies in a Mouse Model. Aging Cell. https://doi.org/10.1111/acel.70145
Vancouver
Du M, Wang Y, Wang X, Liu Y, Xiao F, Zhang J, et al. Age‐Related Complement C3 Drives Memory Impairments and Associated Neuropathologies in a Mouse Model. Aging Cell. 2025. doi:10.1111/acel.70145. PMID: 40539508.
BibTeX
@article{du2025-40539508,
author = {Du, Miaomiao and Wang, Yujia and Wang, Xinyuan and Liu, Yifei and Xiao, Fuchuan and Zhang, Jing and Meng, Xia and Ma, Kunhe and others},
title = {{Age‐Related Complement C3 Drives Memory Impairments and Associated Neuropathologies in a Mouse Model}},
journal = {Aging Cell},
year = {2025},
doi = {10.1111/acel.70145},
pmid = {40539508},
url = {https://doi.org/10.1111/acel.70145}
}
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