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INPP5D modulates TREM2 loss-of-function phenotypes in a β-amyloidosis mouse model
Iguchi A, Takatori S, Kimura S, Muneto H, Wang K, Etani H, Ito G, Sato H et al.. iScience, 2023-03-13
Topic: Brain proteins, microglia and lab models
The genetic associations of TREM2 loss-of-function variants with Alzheimer disease (AD) indicate the protective roles of microglia in AD pathogenesis. Functional deficiencies of TREM2 disrupt microglial clustering around amyloid β (Aβ) plaques, impair their transcriptional response to Aβ, and worsen neuritic dystrophy. However, the molecular mechanism underlying these phenotypes remains unclear. In this study, we investigated the pathological role of another AD risk gene, INPP5D , encoding a phosphoinositide PI(3,4,5)P 3 phosphatase expressed in microglia. In a Tyrobp -deficient TREM2 loss-of-function mouse model, Inpp5d haplodeficiency restored the association of microglia with Aβ plaques, partially restored plaque compaction, and astrogliosis, and reduced phosphorylated tau + dystrophic neurites. Mechanistic analyses suggest that TREM2/TYROBP and INPP5D exert opposing effects on PI(3,4,5)P 3 signaling pathways as well as on phosphoproteins involved in the actin assembly. Our results suggest that INPP5D acts downstream of TREM2/TYROBP to regulate the microglial barrier against Aβ toxicity, thereby modulates Aβ-dependent pathological conversion of tau.
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APA 7th
Iguchi, A., Takatori, S., Kimura, S., Muneto, H., Wang, K., Etani, H., et al. (2023). INPP5D modulates TREM2 loss-of-function phenotypes in a β-amyloidosis mouse model. iScience. https://doi.org/10.1016/j.isci.2023.106375
Vancouver
Iguchi A, Takatori S, Kimura S, Muneto H, Wang K, Etani H, et al. INPP5D modulates TREM2 loss-of-function phenotypes in a β-amyloidosis mouse model. iScience. 2023. doi:10.1016/j.isci.2023.106375. PMID: 37035000.
BibTeX
@article{iguchi2023-37035000,
author = {Iguchi, A. and Takatori, S. and Kimura, S. and Muneto, H. and Wang, K. and Etani, H. and Ito, G. and Sato, H. and others},
title = {{INPP5D modulates TREM2 loss-of-function phenotypes in a β-amyloidosis mouse model}},
journal = {iScience},
year = {2023},
doi = {10.1016/j.isci.2023.106375},
pmid = {37035000},
url = {https://doi.org/10.1016/j.isci.2023.106375}
}
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Key findings
- Mechanistic analyses suggest that TREM2/TYROBP and INPP5D exert opposing effects on PI(3,4,5)P 3 signaling pathways as well as on phosphoproteins involved in the actin assembly.
- Our results suggest that INPP5D acts downstream of TREM2/TYROBP to regulate the microglial barrier against Aβ toxicity, thereby modulates Aβ-dependent pathological conversion of tau.
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Study details
- Evidence strengthLow
How this study scored 40/100
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 and multi-centre collaboration, so those were left out: it earned 23 of the 58 points we could judge it on, which is 40 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (iScience) |
| 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 | 3 / 5 | 2023 — within 6 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 | — / 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 37035000) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 23 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 23 of the 58 points we could judge it on is 40 out of 100. |
| Total | 40 / 100 | — |
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