Home › Research › TREM2 and immune genetics
APOE and TREM2 regulate amyloid-responsive microglia in Alzheimer's disease
Nguyen AT, Wang K, Hu G, Wang X, Miao Z, Azevedo JA, Suh E, Van Deerlin VM et al.. Acta neuropathologica, 2020-08-25
Topic: Brain proteins, microglia and lab models
Beta-amyloid deposition is a defining feature of Alzheimer's disease (AD). How genetic risk factors, like APOE and TREM2, intersect with cellular responses to beta-amyloid in human tissues is not fully understood. Using single-nucleus RNA sequencing of postmortem human brain with varied APOE and TREM2 genotypes and neuropathology, we identified distinct microglia subpopulations, including a subpopulation of CD163-positive amyloid-responsive microglia (ARM) that are depleted in cases with APOE and TREM2 risk variants.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Nguyen, A. T., Wang, K., Hu, G., Wang, X., Miao, Z., Azevedo, J. A., et al. (2020). APOE and TREM2 regulate amyloid-responsive microglia in Alzheimer's disease. Acta neuropathologica. https://doi.org/10.1007/s00401-020-02200-3
Vancouver
Nguyen AT, Wang K, Hu G, Wang X, Miao Z, Azevedo JA, et al. APOE and TREM2 regulate amyloid-responsive microglia in Alzheimer's disease. Acta neuropathologica. 2020. doi:10.1007/s00401-020-02200-3. PMID: 32840654.
BibTeX
@article{nguyen2020-32840654,
author = {Nguyen, A. T. and Wang, K. and Hu, G. and Wang, X. and Miao, Z. and Azevedo, J. A. and Suh, E. and Van Deerlin, V. M. and others},
title = {{APOE and TREM2 regulate amyloid-responsive microglia in Alzheimer's disease}},
journal = {Acta neuropathologica},
year = {2020},
doi = {10.1007/s00401-020-02200-3},
pmid = {32840654},
url = {https://doi.org/10.1007/s00401-020-02200-3}
}
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.
Key findings
- How genetic risk factors, like APOE and TREM2, intersect with cellular responses to beta-amyloid in human tissues is not fully understood.
- Using single-nucleus RNA sequencing of postmortem human brain with varied APOE and TREM2 genotypes and neuropathology, we identified distinct microglia subpopulations, including a subpopulation of CD163-positive amyloid-responsive microglia (ARM) that are depleted in cases with APOE and TREM2 risk variants.
- We validated our single-nucleus RNA sequencing findings in an expanded cohort of AD cases, demonstrating that APOE and TREM2 risk variants are associated with a significant reduction in CD163-positive amyloid-responsive microglia.
- Our results showcase the diverse microglial response in AD and underscore how genetic risk factors influence cellular responses to underlying pathologies.
Why it matters
In postmortem human brain tissue, single-nucleus RNA sequencing found a group of CD163-positive "amyloid-responsive" microglia, the brain's immune cells, that were scarcer in people carrying APOE or TREM2 risk variants. A larger set of Alzheimer's cases confirmed that these risk variants are associated with a significant reduction in these cells. This is an observational, after-death finding about how genetic risk may shape the brain's immune response to amyloid, not evidence for any treatment.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Evidence strengthModerate
How this study scored 56/100
Published in a leading specialty 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 | 9 / 10 | Tier 2 — leading specialty journal (Acta neuropathologica) |
| Journal's citation record | 3 / 4 | Acta Neuropathologica: journal h-index 287 (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 | 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 | 2020 — 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 | 5 / 7 | Cited 253 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 31.6 citations a year over 8 year(s) since 2020 |
| Impact for its field and year | 4 / 6 | Cited 9.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 12 other studies in this library |
| Still being cited | 3 / 4 | Cited 139 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Edward B. Lee: h-index 79 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Pennsylvania: institution h-index 1,859 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 32840654) |
| Free to read | 2 / 2 | Free to read |
| Total | 56 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 25.
Later studies that cite this one
12 studies in the alzhub library list this one in their references. Showing the 8 highest-scoring.
Related studies in TREM2 and immune genetics
Also tagged “macrophages”
363 studies in the library carry the topic tag “macrophages”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 363 tagged studies.