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Trem2 deletion enhances tau dispersion and pathology through microglia exosomes
Zhu B, Liu Y, Hwang S, Archuleta K, Huang H, Campos A, Murad R, Piña-Crespo J et al.. Molecular neurodegeneration, 2022-09-02
Topic: Brain proteins, microglia and lab models
Background Alzheimer's disease (AD) is a neurodegenerative disorder that manifests sequential Aβ and tau brain pathology with age-dependent onset. Variants in the microglial immune receptor TREM2 are associated with enhanced risk of onset in sporadic Alzheimer's disease (AD). While recent studies suggest TREM2 dysfunction can aggravate tau pathology, mechanisms underlying TREM2-dependent modulation of tau pathology remains elusive.
Key findings
- Variants in the microglial immune receptor TREM2 are associated with enhanced risk of onset in sporadic Alzheimer's disease (AD).
- While recent studies suggest TREM2 dysfunction can aggravate tau pathology, mechanisms underlying TREM2-dependent modulation of tau pathology remains elusive.
- Methods Here, we characterized differences in progressive tau spreading from the medial entorhinal cortex (MEC) to the hippocampus in wildtype (WT) and Trem2 knockout (KO) mice by injection of AAV-P301L tau into the MEC, and correlated changes in hippocampal tau histopathology with spatial and fear memory.
- We also compared effects of intraneuronal dispersion between cultured microglia and neurons using a microfluidic dispersion assay, analyzed differences in microglial tau trafficking following uptake, and quantified exosomal tau secretion and pathogenicity from purified WT and Trem2 KO exosomes.
Why it matters
In mice, deleting Trem2 increased the spread of tau and tau pathology through microglia exosomes. This is animal work identifying a mechanism, not a proven treatment for people.
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Study details
- Evidence strengthLow
How this study scored 48/100
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 (Molecular neurodegeneration) |
| Journal's citation record | 2 / 4 | Molecular Neurodegeneration: journal h-index 164 (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 | 2022 — 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) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 123 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 20.5 citations a year over 6 year(s) since 2022 |
| Impact for its field and year | 4 / 6 | Cited 12.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 3 other studies in this library |
| Still being cited | 3 / 4 | Cited 94 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Timothy Y. Huang: h-index 33 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Sanford Burnham Prebys Medical Discovery Institute: institution h-index 676 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 36056435) |
| Free to read | 2 / 2 | Free to read |
| Total | 48 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1186/s13024-022-00562-8
- PubMed: 36056435
- Original source →
- Free full text: Molecular Neurodegeneration →
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
Zhu, B., Liu, Y., Hwang, S., Archuleta, K., Huang, H., Campos, A., et al. (2022). Trem2 deletion enhances tau dispersion and pathology through microglia exosomes. Molecular neurodegeneration. https://doi.org/10.1186/s13024-022-00562-8
Vancouver
Zhu B, Liu Y, Hwang S, Archuleta K, Huang H, Campos A, et al. Trem2 deletion enhances tau dispersion and pathology through microglia exosomes. Molecular neurodegeneration. 2022. doi:10.1186/s13024-022-00562-8. PMID: 36056435.
BibTeX
@article{zhu2022-36056435,
author = {Zhu, B. and Liu, Y. and Hwang, S. and Archuleta, K. and Huang, H. and Campos, A. and Murad, R. and Piña-Crespo, J. and others},
title = {{Trem2 deletion enhances tau dispersion and pathology through microglia exosomes}},
journal = {Molecular neurodegeneration},
year = {2022},
doi = {10.1186/s13024-022-00562-8},
pmid = {36056435},
url = {https://doi.org/10.1186/s13024-022-00562-8}
}
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