The TREM-receptor family interactome in the human brain
de Kleijn K, Weller S, Klaassen R, Koopmans F, Smit A, Wijdeven R.. bioRxiv, 2026-10-29
Topic: Inflammation, microglia and astrocytes
The Triggering Receptors Expressed on Myeloid cells (TREMs) are a family of cell-surface receptors instrumental in the activation of different myeloid cells. TREM2, its most studied member, is genetically linked to Alzheimer disease (AD), and its interactions with BAmyloid; and APOE have placed it at the forefront of microglia dysfunction in the brain. However, the ligands and binding partners of the other TREM members (TREM1, TREML1, TREML2 and TREML4) are less well defined. Here, we used human AD and non-AD brain lysate to profile the interactome of the ligand binding domains of the different TREM receptors. Besides identifying known ligands for TREM1 (PGLYRP1), TREM2 (C1QL3, LGALSL) and TREML1 (Fibrinogens), we identified complement components and the apolipoproteins APOA1 and APOA4 as novel interactors of TREML1, and heparan sulfate modified proteins as binding partners for TREML2. Furthermore, similar to TREM2, all the TREMLs interacted with the apolipoproteins APOE and Clusterin. Using in vitro pulldowns with heparin, we confirmed that specifically TREML2 interacted with heparan sulfates, in a manner unaffected by the AD-linked S144G mutation. Together, our proteomics approach identified novel interactors for TREML1 and TREML2, cementing the role of the different TREM-proteins in lipid trafficking and immunity.
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APA 7th
de Kleijn, K., Weller, S., Klaassen, R., Koopmans, F., Smit, A., & Wijdeven, R. (2026). The TREM-receptor family interactome in the human brain. bioRxiv. https://doi.org/10.64898/2026.10.28.762136
Vancouver
de Kleijn K, Weller S, Klaassen R, Koopmans F, Smit A, Wijdeven R. The TREM-receptor family interactome in the human brain. bioRxiv. 2026. doi:10.64898/2026.10.28.762136.
BibTeX
@article{dekleijn2026-4fee9899,
author = {de Kleijn, K. and Weller, S. and Klaassen, R. and Koopmans, F. and Smit, A. and Wijdeven, R.},
title = {{The TREM-receptor family interactome in the human brain}},
journal = {bioRxiv},
year = {2026},
doi = {10.64898/2026.10.28.762136},
url = {https://doi.org/10.64898/2026.10.28.762136}
}
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Key findings
- Here, we used human AD and non-AD brain lysate to profile the interactome of the ligand binding domains of the different TREM receptors.
- Besides identifying known ligands for TREM1 (PGLYRP1), TREM2 (C1QL3, LGALSL) and TREML1 (Fibrinogens), we identified complement components and the apolipoproteins APOA1 and APOA4 as novel interactors of TREML1, and heparan sulfate modified proteins as binding partners for TREML2.
- Furthermore, similar to TREM2, all the TREMLs interacted with the apolipoproteins APOE and Clusterin.
- Using in vitro pulldowns with heparin, we confirmed that specifically TREML2 interacted with heparan sulfates, in a manner unaffected by the AD-linked S144G mutation.
- Together, our proteomics approach identified novel interactors for TREML1 and TREML2, cementing the role of the different TREM-proteins in lipid trafficking and immunity.
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Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 21 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 13 of the 62 points we could judge it on, which is 21 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (bioRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| 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 | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 13 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 13 of the 62 points we could judge it on is 21 out of 100. |
| Total | 21 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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