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PCSK9 ablation attenuates Aβ pathology, neuroinflammation and cognitive dysfunctions in 5XFAD mice
Antonietta Vilella, Martina Bodria, Bianca Papotti, Ilaria Zanotti, Francesca Zimetti, Giulia Remaggi, Lisa Elviri, Francesco Potì et al.. Brain, behavior, and immunity, 2023-11-13
Topic: Inflammation, microglia and astrocytes
In vitro, PCSK9 significantly increased IL6, IL1B and TNFΑ mRNA levels in Aβ fibrils-treated U373 cells, without influencing inflammasome gene expression, except for an increase in NLRC4 mRNA levels. In vivo, PCSK9 ablation in 5XFAD mice significantly improved the performance at the Morris water maze test; these changes were accompanied by a reduced corticohippocampal Aβ burden without affecting plaque spatial/regional distribution and composition or global BACE1 expression. Furthermore, PCSK9 loss in 5XFAD mice induced decreased microgliosis and astrocyte reactivity in several brain regions. Conversely, knocking out PCSK9 had minimal impact on brain cholesterol and hydroxysterol levels. In vitro studies showed a pro-inflammatory effect of PCSK9. Consistently, in vivo data indicated a protective role of PCSK9 ablation against cognitive impairments, associated with improved Aβ pathology and attenuated neuroinflammation in a severe mouse model of AD. PCSK9 may thus be considered a novel pharmacological target for the treatment of AD.
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APA 7th
Vilella, A., Bodria, M., Papotti, B., Zanotti, I., Zimetti, F., Remaggi, G., et al. (2024). PCSK9 ablation attenuates Aβ pathology, neuroinflammation and cognitive dysfunctions in 5XFAD mice. Brain, behavior, and immunity. https://doi.org/10.1016/j.bbi.2023.11.008
Vancouver
Vilella A, Bodria M, Papotti B, Zanotti I, Zimetti F, Remaggi G, et al. PCSK9 ablation attenuates Aβ pathology, neuroinflammation and cognitive dysfunctions in 5XFAD mice. Brain, behavior, and immunity. 2024. doi:10.1016/j.bbi.2023.11.008. PMID: 37967665.
BibTeX
@article{vilella2024-37967665,
author = {Vilella, Antonietta and Bodria, Martina and Papotti, Bianca and Zanotti, Ilaria and Zimetti, Francesca and Remaggi, Giulia and Elviri, Lisa and Potì, Francesco and others},
title = {{PCSK9 ablation attenuates Aβ pathology, neuroinflammation and cognitive dysfunctions in 5XFAD mice}},
journal = {Brain, behavior, and immunity},
year = {2024},
doi = {10.1016/j.bbi.2023.11.008},
pmid = {37967665},
url = {https://doi.org/10.1016/j.bbi.2023.11.008}
}
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Key findings
- In vitro, PCSK9 significantly increased IL6, IL1B and TNFΑ mRNA levels in Aβ fibrils-treated U373 cells, without influencing inflammasome gene expression, except for an increase in NLRC4 mRNA levels.
- In vivo, PCSK9 ablation in 5XFAD mice significantly improved the performance at the Morris water maze test; these changes were accompanied by a reduced corticohippocampal Aβ burden without affecting plaque spatial/regional distribution and composition or global BACE1 expression.
- Furthermore, PCSK9 loss in 5XFAD mice induced decreased microgliosis and astrocyte reactivity in several brain regions.
- Conversely, knocking out PCSK9 had minimal impact on brain cholesterol and hydroxysterol levels.
- In vitro studies showed a pro-inflammatory effect of PCSK9.
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 (Brain, behavior, and immunity) |
| 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 | 2024 — 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 37967665) |
| 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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