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TREM2 Acts Downstream of CD33 in Modulating Microglial Pathology in Alzheimer's Disease
Griciuc A, Patel S, Federico AN, Choi SH, Innes BJ, Oram MK, Cereghetti G, McGinty D et al.. Neuron, 2019-07-10
Topic: Brain proteins, microglia and lab models
The microglial receptors CD33 and TREM2 have been associated with risk for Alzheimer's disease (AD). Here, we investigated crosstalk between CD33 and TREM2. We showed that knockout of CD33 attenuated amyloid beta (Aβ) pathology and improved cognition in 5xFAD mice, both of which were abrogated by additional TREM2 knockout.
Key findings
- Here, we investigated crosstalk between CD33 and TREM2.
- We showed that knockout of CD33 attenuated amyloid beta (Aβ) pathology and improved cognition in 5xFAD mice, both of which were abrogated by additional TREM2 knockout.
- Knocking out TREM2 in 5xFAD mice exacerbated Aβ pathology and neurodegeneration but reduced Iba1 + cell numbers, all of which could not be rescued by additional CD33 knockout.
- RNA-seq profiling of microglia revealed that genes related to phagocytosis and signaling (IL-6, IL-8, acute phase response) are upregulated in 5xFAD;CD33 -/- and downregulated in 5xFAD;TREM2 -/- mice.
Why it matters
In mice bred to build up amyloid (5xFAD), removing the microglial receptor CD33 reduced amyloid pathology and improved cognition, but only while TREM2 was present: also removing TREM2 cancelled both effects, and removing TREM2 alone worsened amyloid pathology and neurodegeneration, which CD33 removal could not rescue. Microglial genes for phagocytosis and signalling (IL-6, IL-8, acute phase response) went up without CD33 and down without TREM2, which the authors summarise as TREM2 acting downstream of CD33. These are mouse findings with no numbers given in the record; they do not show that changing CD33 or TREM2 would treat or prevent Alzheimer's disease in people.
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Study details
- Evidence strengthLow
How this study scored 56/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neuron) |
| Journal's citation record | 4 / 4 | Neuron: journal h-index 689 (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 | 2019 — 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 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 380 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 42.2 citations a year over 9 year(s) since 2019 |
| 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 | 4 / 6 | Cited by 36 other studies in this library |
| Still being cited | 3 / 4 | Cited 154 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Rudolph E. Tanzi: h-index 145 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 31301936) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 56 / 100 | — |
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Read the original
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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
Griciuc, A., Patel, S., Federico, A. N., Choi, S. H., Innes, B. J., Oram, M. K., et al. (2019). TREM2 Acts Downstream of CD33 in Modulating Microglial Pathology in Alzheimer's Disease. Neuron. https://doi.org/10.1016/j.neuron.2019.06.010
Vancouver
Griciuc A, Patel S, Federico AN, Choi SH, Innes BJ, Oram MK, et al. TREM2 Acts Downstream of CD33 in Modulating Microglial Pathology in Alzheimer's Disease. Neuron. 2019. doi:10.1016/j.neuron.2019.06.010. PMID: 31301936.
BibTeX
@article{griciuc2019-31301936,
author = {Griciuc, A. and Patel, S. and Federico, A. N. and Choi, S. H. and Innes, B. J. and Oram, M. K. and Cereghetti, G. and McGinty, D. and others},
title = {{TREM2 Acts Downstream of CD33 in Modulating Microglial Pathology in Alzheimer's Disease}},
journal = {Neuron},
year = {2019},
doi = {10.1016/j.neuron.2019.06.010},
pmid = {31301936},
url = {https://doi.org/10.1016/j.neuron.2019.06.010}
}
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