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KChIP3 fosters neuroinflammation and synaptic dysfunction in the 5XFAD mouse model of Alzheimer's disease
Bolivar Arcos-Encarnación, Eladio Cortes-Flores, Isabel Barón-Mendoza, Jorge Luis Almazán, David Valle-García, Sol Díaz de León-Guerrero, Ladislav Hovan, Karla F Meza-Sosa et al.. Journal of neuroinflammation, 2025-06-19
Topic: Inflammation, microglia and astrocytes
Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by β-amyloid (βA) accumulation, neuroinflammation, excessive synaptic pruning, and cognitive decline. Despite extensive research, effective treatments remain elusive. Here, we identify potassium channel-interacting protein 3 (KChIP3) as a key driver of AD pathology using the 5XFAD mouse model. KChIP3 levels were significantly elevated in the hippocampus of 5XFAD mice, correlating with βA burden and neuroinflammation. This upregulation was triggered by inflammatory signaling via the NLRP3 inflammasome and Caspase-1 activation. Notably, genetic deletion of KChIP3 (5XFAD/KChIP3-/-) markedly reduced βA plaque deposition, pro-inflammatory cytokines, reactive gliosis, and expression of inflammation-related proteins (APO, CLU, MDK). Transcriptomic and proteomic analyses revealed restored synaptic markers (CD47, CD200, CACNB4, GDA) and a shift of the disease-associated microglial (DAM-1) phenotype. Mechanistically, we propose that KChIP3 amplifies AD pathology through two key mechanisms: (1) sustaining neuroinflammation by upregulating pro-inflammatory genes and (2) impairing synaptic integrity by repressing genes critical for neuronal function. Consistently, KChIP3 deletion enhanced dendritic complexity, synaptic plasticity, and cognitive performance in 5XFAD mice. These findings position KChIP3 as a potential therapeutic target for mitigating neuroinflammation and synaptic dysfunction in AD and highlight its potential as a biomarker for disease progression.
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APA 7th
Arcos-Encarnación, B., Cortes-Flores, E., Barón-Mendoza, I., Almazán, J. L., Valle-García, D., de León-Guerrero, S. D., et al. (2025). KChIP3 fosters neuroinflammation and synaptic dysfunction in the 5XFAD mouse model of Alzheimer's disease. Journal of neuroinflammation. https://doi.org/10.1186/s12974-025-03426-2
Vancouver
Arcos-Encarnación B, Cortes-Flores E, Barón-Mendoza I, Almazán JL, Valle-García D, de León-Guerrero SD, et al. KChIP3 fosters neuroinflammation and synaptic dysfunction in the 5XFAD mouse model of Alzheimer's disease. Journal of neuroinflammation. 2025. doi:10.1186/s12974-025-03426-2. PMID: 40537787.
BibTeX
@article{arcosencarnacion2025-40537787,
author = {Arcos-Encarnación, Bolivar and Cortes-Flores, Eladio and Barón-Mendoza, Isabel and Almazán, Jorge Luis and Valle-García, David and de León-Guerrero, Sol Díaz and Hovan, Ladislav and Meza-Sosa, Karla F and others},
title = {{KChIP3 fosters neuroinflammation and synaptic dysfunction in the 5XFAD mouse model of Alzheimer's disease}},
journal = {Journal of neuroinflammation},
year = {2025},
doi = {10.1186/s12974-025-03426-2},
pmid = {40537787},
url = {https://doi.org/10.1186/s12974-025-03426-2}
}
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Key findings
- KChIP3 levels were significantly elevated in the hippocampus of 5XFAD mice, correlating with βA burden and neuroinflammation.
- Transcriptomic and proteomic analyses revealed restored synaptic markers (CD47, CD200, CACNB4, GDA) and a shift of the disease-associated microglial (DAM-1) phenotype.
- These findings position KChIP3 as a potential therapeutic target for mitigating neuroinflammation and synaptic dysfunction in AD and highlight its potential as a biomarker for disease progression.
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 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 (Journal of neuroinflammation) |
| 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 | Laboratory or animal study (title names “5xfad”) — scores zero |
| 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 40537787) |
| 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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