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SFRP1 upregulation causes hippocampal synaptic dysfunction and memory impairment
Guadalupe Pereyra, María Inés Mateo, Pablo Miaja, María Jesús Martin-Bermejo, Marcos Martinez-Baños, Remco Klaassen, Agnès Gruart, Javier Rueda-Carrasco et al.. Cell reports, 2025-04-07
Topic: Disease mechanisms in lab and animal studies
Impaired neuronal and synaptic function are hallmarks of early Alzheimer's disease (AD), preceding other neuropathological traits and cognitive decline. We previously showed that SFRP1, a glial-derived protein elevated in AD brains from preclinical stages, contributes to disease progression, implicating glial factors in early pathogenesis. Here, we generate and analyze transgenic mice overexpressing astrocytic SFRP1. SFRP1 accumulation causes early dendritic and synaptic defects in adult mice, followed by impaired synaptic long-term potentiation and cognitive decline, evident only when the animals age, thereby mimicking AD's structural-functional temporal distinction. This phenotype correlates with proteomic changes, including increased structural synaptic proteins like neurexin, which localizes in close proximity with SFRP1 in cultured hippocampal neurons. We conclude that excessive SFRP1 hinders synaptic protein turnover, reducing synaptic plasticity-a mechanism that may underlie the synaptopathy observed in the brains of prodromal AD patients.
Key findings
- We previously showed that SFRP1, a glial-derived protein elevated in AD brains from preclinical stages, contributes to disease progression, implicating glial factors in early pathogenesis.
- We conclude that excessive SFRP1 hinders synaptic protein turnover, reducing synaptic plasticity-a mechanism that may underlie the synaptopathy observed in the brains of prodromal AD patients.
Study details
- Evidence strengthLow
How this study scored 43/100
Published in a peer-reviewed 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 journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 24 of the 56 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Cell reports) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40198223) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 24 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 24 of the 56 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
What each of these 20 components measures, and what this score is not →
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APA 7th
Pereyra, G., Mateo, M. I., Miaja, P., Martin-Bermejo, M. J., Martinez-Baños, M., Klaassen, R., et al. (2025). SFRP1 upregulation causes hippocampal synaptic dysfunction and memory impairment. Cell reports. https://doi.org/10.1016/j.celrep.2025.115535
Vancouver
Pereyra G, Mateo MI, Miaja P, Martin-Bermejo MJ, Martinez-Baños M, Klaassen R, et al. SFRP1 upregulation causes hippocampal synaptic dysfunction and memory impairment. Cell reports. 2025. doi:10.1016/j.celrep.2025.115535. PMID: 40198223.
BibTeX
@article{pereyra2025-40198223,
author = {Pereyra, Guadalupe and Mateo, María Inés and Miaja, Pablo and Martin-Bermejo, María Jesús and Martinez-Baños, Marcos and Klaassen, Remco and Gruart, Agnès and Rueda-Carrasco, Javier and others},
title = {{SFRP1 upregulation causes hippocampal synaptic dysfunction and memory impairment}},
journal = {Cell reports},
year = {2025},
doi = {10.1016/j.celrep.2025.115535},
pmid = {40198223},
url = {https://doi.org/10.1016/j.celrep.2025.115535}
}