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Reactive or transgenic increase in microglial TYROBP reveals a TREM2-independent TYROBP-APOE link in wild-type and Alzheimer's-related mice
Audrain M, Haure-Mirande JV, Mleczko J, Wang M, Griffin JK, St George-Hyslop PH, Fraser P, Zhang B et al.. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2020-12-12
Topic: Brain proteins, microglia and lab models
Introduction Microglial TYROBP (DAP12) is a network hub and driver in sporadic late-onset Alzheimer's disease (AD). TYROBP is a cytoplasmic adaptor for TREM2 and other receptors, but little is known about its roles and actions in AD. Herein, we demonstrate that endogenous Tyrobp transcription is specifically increased in recruited microglia.
Key findings
- TYROBP is a cytoplasmic adaptor for TREM2 and other receptors, but little is known about its roles and actions in AD.
- Herein, we demonstrate that endogenous Tyrobp transcription is specifically increased in recruited microglia.
- Methods Using a novel transgenic mouse overexpressing TYROBP in microglia, we observed a decrease of the amyloid burden and an increase of TAU phosphorylation stoichiometry when crossed with APP/PSEN1 or MAPT P301S mice, respectively.
- Characterization of these mice revealed Tyrobp-related modulation of apolipoprotein E (Apoe) transcription.
Why it matters
In transgenic mice, overexpressing TYROBP in microglia decreased amyloid burden but increased tau phosphorylation, revealing a TREM2-independent TYROBP-APOE link. This is animal research and does not establish a treatment for Alzheimer's disease.
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Study details
- Evidence strengthLow
How this study scored 47/100
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 (Alzheimer's & dementia : the journal of the Alzheimer's Association) |
| Journal's citation record | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (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 | 3 / 5 | 2021 — 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 “transgenic”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 66 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 9.4 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 2 / 6 | Cited 2.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 2 / 4 | Cited 40 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Michelle E. Ehrlich: h-index 59 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Toronto: institution h-index 1,923 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33314529) |
| Free to read | 2 / 2 | Free to read |
| Total | 47 / 100 | — |
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Read the original
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Audrain, M., Haure-Mirande, J. V., Mleczko, J., Wang, M., Griffin, J. K., St George-Hyslop, P. H., et al. (2021). Reactive or transgenic increase in microglial TYROBP reveals a TREM2-independent TYROBP-APOE link in wild-type and Alzheimer's-related mice. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.12256
Vancouver
Audrain M, Haure-Mirande JV, Mleczko J, Wang M, Griffin JK, St George-Hyslop PH, et al. Reactive or transgenic increase in microglial TYROBP reveals a TREM2-independent TYROBP-APOE link in wild-type and Alzheimer's-related mice. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2021. doi:10.1002/alz.12256. PMID: 33314529.
BibTeX
@article{audrain2021-33314529,
author = {Audrain, M. and Haure-Mirande, J. V. and Mleczko, J. and Wang, M. and Griffin, J. K. and St George-Hyslop, P. H. and Fraser, P. and Zhang, B. and others},
title = {{Reactive or transgenic increase in microglial TYROBP reveals a TREM2-independent TYROBP-APOE link in wild-type and Alzheimer's-related mice}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2021},
doi = {10.1002/alz.12256},
pmid = {33314529},
url = {https://doi.org/10.1002/alz.12256}
}
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