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Caspase-1 inhibition alleviates cognitive impairment and neuropathology in an Alzheimer's disease mouse model
Flores J, Noël A, Foveau B, Lynham J, Lecrux C, LeBlanc AC.. Nature communications, 2018-09-25
Topic: Brain proteins, microglia and lab models
Alzheimer's disease (AD) is an intractable progressive neurodegenerative disease characterized by cognitive decline and dementia. An inflammatory neurodegenerative pathway, involving Caspase-1 activation, is associated with human age-dependent cognitive impairment and several classical AD brain pathologies. Here, we show that the nontoxic and blood-brain barrier permeable small molecule Caspase-1 inhibitor VX-765 dose-dependently reverses episodic and spatial memory impairment, and hyperactivity in the J20 mouse model of AD.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Flores, J., Noël, A., Foveau, B., Lynham, J., Lecrux, C., & LeBlanc, A. C. (2018). Caspase-1 inhibition alleviates cognitive impairment and neuropathology in an Alzheimer's disease mouse model. Nature communications. https://doi.org/10.1038/s41467-018-06449-x
Vancouver
Flores J, Noël A, Foveau B, Lynham J, Lecrux C, LeBlanc AC. Caspase-1 inhibition alleviates cognitive impairment and neuropathology in an Alzheimer's disease mouse model. Nature communications. 2018. doi:10.1038/s41467-018-06449-x. PMID: 30254377.
BibTeX
@article{flores2018-30254377,
author = {Flores, J. and Noël, A. and Foveau, B. and Lynham, J. and Lecrux, C. and LeBlanc, A. C.},
title = {{Caspase-1 inhibition alleviates cognitive impairment and neuropathology in an Alzheimer's disease mouse model}},
journal = {Nature communications},
year = {2018},
doi = {10.1038/s41467-018-06449-x},
pmid = {30254377},
url = {https://doi.org/10.1038/s41467-018-06449-x}
}
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Key findings
- An inflammatory neurodegenerative pathway, involving Caspase-1 activation, is associated with human age-dependent cognitive impairment and several classical AD brain pathologies.
- Here, we show that the nontoxic and blood-brain barrier permeable small molecule Caspase-1 inhibitor VX-765 dose-dependently reverses episodic and spatial memory impairment, and hyperactivity in the J20 mouse model of AD.
- Cessation of VX-765 results in the reappearance of memory deficits in the mice after 1 month and recommencement of treatment re-establishes normal cognition.
- VX-765 prevents progressive amyloid beta peptide deposition, reverses brain inflammation, and normalizes synaptophysin protein levels in mouse hippocampus.
Why it matters
In a mouse model of Alzheimer's disease, the Caspase-1 inhibitor VX-765 reversed memory impairment and hyperactivity, but memory deficits returned about a month after the drug was stopped. This is early animal research, so it does not yet show that the drug would work or be safe in people.
Study details
- Evidence strengthLow
How this study scored 52/100
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 communications) |
| Journal's citation record | 4 / 4 | Nature Communications: journal h-index 747 (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 | 2 / 5 | 2018 — within 10 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 | 5 / 7 | Cited 287 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 28.7 citations a year over 10 year(s) since 2018 |
| Impact for its field and year | 4 / 6 | Cited 16.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 5 other studies in this library |
| Still being cited | 3 / 4 | Cited 94 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Andrea Claire LeBlanc: h-index 48 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | McGill University: institution h-index 1,373 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 30254377) |
| Free to read | 2 / 2 | Free to read |
| Total | 52 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1038/s41467-018-06449-x
- PubMed: 30254377
- Original source →
- Free full text: Nature Communications →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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