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Human early-onset dementia caused by DAP12 deficiency reveals a unique signature of dysregulated microglia
Zhou Y, Tada M, Cai Z, Andhey PS, Swain A, Miller KR, Gilfillan S, Artyomov MN et al.. Nature immunology, 2023-01-19
Topic: Brain proteins, microglia and lab models
The TREM2-DAP12 receptor complex sustains microglia functions. Heterozygous hypofunctional TREM2 variants impair microglia, accelerating late-onset Alzheimer's disease. Homozygous inactivating variants of TREM2 or TYROBP-encoding DAP12 cause Nasu-Hakola disease (NHD), an early-onset dementia characterized by cerebral atrophy, myelin loss and gliosis.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Zhou, Y., Tada, M., Cai, Z., Andhey, P. S., Swain, A., Miller, K. R., et al. (2023). Human early-onset dementia caused by DAP12 deficiency reveals a unique signature of dysregulated microglia. Nature immunology. https://doi.org/10.1038/s41590-022-01403-y
Vancouver
Zhou Y, Tada M, Cai Z, Andhey PS, Swain A, Miller KR, et al. Human early-onset dementia caused by DAP12 deficiency reveals a unique signature of dysregulated microglia. Nature immunology. 2023. doi:10.1038/s41590-022-01403-y. PMID: 36658241.
BibTeX
@article{zhou2023-36658241,
author = {Zhou, Y. and Tada, M. and Cai, Z. and Andhey, P. S. and Swain, A. and Miller, K. R. and Gilfillan, S. and Artyomov, M. N. and others},
title = {{Human early-onset dementia caused by DAP12 deficiency reveals a unique signature of dysregulated microglia}},
journal = {Nature immunology},
year = {2023},
doi = {10.1038/s41590-022-01403-y},
pmid = {36658241},
url = {https://doi.org/10.1038/s41590-022-01403-y}
}
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Key findings
- Heterozygous hypofunctional TREM2 variants impair microglia, accelerating late-onset Alzheimer's disease.
- Homozygous inactivating variants of TREM2 or TYROBP-encoding DAP12 cause Nasu-Hakola disease (NHD), an early-onset dementia characterized by cerebral atrophy, myelin loss and gliosis.
- Here, single-nucleus RNA-sequencing analysis of brain specimens from DAP12-deficient NHD individuals revealed a unique microglia signature indicating heightened RUNX1, STAT3 and transforming growth factor-β signaling pathways that mediate repair responses to injuries.
- This profile correlated with a wound healing signature in astrocytes and impaired myelination in oligodendrocytes, while pericyte profiles indicated vascular abnormalities.
Why it matters
Single-nucleus RNA-sequencing of brain specimens from people with DAP12-deficient Nasu-Hakola disease revealed a unique microglia signature. It describes a rare early-onset dementia and does not test a treatment or cure for Alzheimer's disease.
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Study details
- Evidence strengthLow
How this study scored 50/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Nature immunology) |
| Journal's citation record | 4 / 4 | Nature Immunology: journal h-index 526 (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 | 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 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 59 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 11.8 citations a year over 5 year(s) since 2023 |
| Impact for its field and year | 3 / 6 | Cited 4.9× 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 50 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Marco Colonna: h-index 172 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Washington University in St. Louis: institution h-index 1,962 (OpenAlex) |
| Multicenter collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 36658241) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 50 / 100 | — |
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