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Defects in lysosomal function and lipid metabolism in human microglia harboring a TREM2 loss of function mutation
Filipello F, You SF, Mirfakhar FS, Mahali S, Bollman B, Acquarone M, Korvatska O, Marsh JA et al.. Acta neuropathologica, 2023-04-28
Topic: Brain proteins, microglia and lab models
TREM2 is an innate immune receptor expressed by microglia in the adult brain. Genetic variation in the TREM2 gene has been implicated in risk for Alzheimer's disease and frontotemporal dementia, while homozygous TREM2 mutations cause a rare leukodystrophy, Nasu-Hakola disease (NHD). Despite extensive investigation, the role of TREM2 in NHD pathogenesis remains poorly understood.
Key findings
- Genetic variation in the TREM2 gene has been implicated in risk for Alzheimer's disease and frontotemporal dementia, while homozygous TREM2 mutations cause a rare leukodystrophy, Nasu-Hakola disease (NHD).
- Despite extensive investigation, the role of TREM2 in NHD pathogenesis remains poorly understood.
- Here, we investigate the mechanisms by which a homozygous stop-gain TREM2 mutation (p.Q33X) contributes to NHD.
- Induced pluripotent stem cell (iPSC)-derived microglia (iMGLs) were generated from two NHD families: three homozygous TREM2 p.Q33X mutation carriers (termed NHD), two heterozygous mutation carriers, one related non-carrier, and two unrelated non-carriers.
Why it matters
Microglia made from patient cells carrying a TREM2 loss-of-function mutation showed defects in lysosomal function and lipid metabolism. This is laboratory cell work on a rare genetic disease and does not show that any treatment prevents or cures Alzheimer's disease.
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Study details
- Evidence strengthLow
How this study scored 53/100
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 | 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 | 2023 — 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 | 4 / 7 | Cited 76 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 15.2 citations a year over 5 year(s) since 2023 |
| Impact for its field and year | 3 / 6 | Cited 6.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 4 other studies in this library |
| Still being cited | 3 / 4 | Cited 69 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Celeste M M. Karch: h-index 67 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 37115208) |
| Free to read | 2 / 2 | Free to read |
| Total | 53 / 100 | — |
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Read the original
- DOI: 10.1007/s00401-023-02568-y
- PubMed: 37115208
- Original source →
- Free full text: Acta Neuropathologica →
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
Filipello, F., You, S. F., Mirfakhar, F. S., Mahali, S., Bollman, B., Acquarone, M., et al. (2023). Defects in lysosomal function and lipid metabolism in human microglia harboring a TREM2 loss of function mutation. Acta neuropathologica. https://doi.org/10.1007/s00401-023-02568-y
Vancouver
Filipello F, You SF, Mirfakhar FS, Mahali S, Bollman B, Acquarone M, et al. Defects in lysosomal function and lipid metabolism in human microglia harboring a TREM2 loss of function mutation. Acta neuropathologica. 2023. doi:10.1007/s00401-023-02568-y. PMID: 37115208.
BibTeX
@article{filipello2023-37115208,
author = {Filipello, F. and You, S. F. and Mirfakhar, F. S. and Mahali, S. and Bollman, B. and Acquarone, M. and Korvatska, O. and Marsh, J. A. and others},
title = {{Defects in lysosomal function and lipid metabolism in human microglia harboring a TREM2 loss of function mutation}},
journal = {Acta neuropathologica},
year = {2023},
doi = {10.1007/s00401-023-02568-y},
pmid = {37115208},
url = {https://doi.org/10.1007/s00401-023-02568-y}
}
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