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Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE
Parhizkar S, Arzberger T, Brendel M, Kleinberger G, Deussing M, Focke C, Nuscher B, Xiong M et al.. Nature neuroscience, 2019-01-07
Topic: Brain proteins, microglia and lab models
Coding variants in the triggering receptor expressed on myeloid cells 2 (TREM2) are associated with late-onset Alzheimer's disease (AD). We demonstrate that amyloid plaque seeding is increased in the absence of functional Trem2. Increased seeding is accompanied by decreased microglial clustering around newly seeded plaques and reduced plaque-associated apolipoprotein E (ApoE).
Key findings
- We demonstrate that amyloid plaque seeding is increased in the absence of functional Trem2.
- Increased seeding is accompanied by decreased microglial clustering around newly seeded plaques and reduced plaque-associated apolipoprotein E (ApoE).
- Reduced ApoE deposition in plaques is also observed in brains of AD patients carrying TREM2 coding variants.
- Proteomic analyses and microglia depletion experiments revealed microglia as one origin of plaque-associated ApoE.
Why it matters
In mice, losing TREM2 function increased the early seeding of amyloid plaques and reduced microglial clustering and ApoE around new plaques. This suggests TREM2 and microglia affect how amyloid plaques begin to form, but it is animal and human tissue work, not a treatment.
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Study details
- Study designlongitudinal study
- Evidence strengthModerate
How this study scored 71/100
Published in a leading specialty journal, and it is a longitudinal study following the same people over time. Scored zero for sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 68 of the 96 points we could judge it on, which is 71 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature neuroscience) |
| Journal's citation record | 4 / 4 | Nature Neuroscience: journal h-index 593 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A longitudinal study following the same people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” 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 555 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 61.7 citations a year over 9 year(s) since 2019 |
| Impact for its field and year | 5 / 6 | Cited 29.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 83 other studies in this library |
| Still being cited | 3 / 4 | Cited 183 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 18 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 30617257) |
| Free to read | 2 / 2 | Free to read |
| Points | 68 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 68 of the 96 points we could judge it on is 71 out of 100. |
| Total | 71 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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
Parhizkar, S., Arzberger, T., Brendel, M., Kleinberger, G., Deussing, M., Focke, C., et al. (2019). Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE. Nature neuroscience. https://doi.org/10.1038/s41593-018-0296-9
Vancouver
Parhizkar S, Arzberger T, Brendel M, Kleinberger G, Deussing M, Focke C, et al. Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE. Nature neuroscience. 2019. doi:10.1038/s41593-018-0296-9. PMID: 30617257.
BibTeX
@article{parhizkar2019-30617257,
author = {Parhizkar, S. and Arzberger, T. and Brendel, M. and Kleinberger, G. and Deussing, M. and Focke, C. and Nuscher, B. and Xiong, M. and others},
title = {{Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE}},
journal = {Nature neuroscience},
year = {2019},
doi = {10.1038/s41593-018-0296-9},
pmid = {30617257},
url = {https://doi.org/10.1038/s41593-018-0296-9}
}
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