Topic: Brain proteins, microglia and lab models
This molecular genetics study found that several TREM2 gene variants previously thought to work only by altering the TREM2 protein itself, also disrupt how the TREM2 gene's RNA message is spliced together, sometimes producing dysfunctional protein versions. The two most common Alzheimer's risk variants (R62H and T96K) both increased abnormal 'exon skipping', confirmed in human brain tissue from three separate cohorts.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Kiianitsa, K., Lukes, M. E., Hayes, B. J., Brutman, J. N., Valdmanis, P. N., Bird, T. D., et al. (2024). TREM2 variants that cause early dementia and increase Alzheimer's disease risk affect gene splicing. Brain.
Vancouver
Kiianitsa K, Lukes ME, Hayes BJ, Brutman JN, Valdmanis PN, Bird TD, et al. TREM2 variants that cause early dementia and increase Alzheimer's disease risk affect gene splicing. Brain. 2024.
BibTeX
@article{kiianitsa2024-9e48f8fa,
author = {Kiianitsa, K. and Lukes, M. E. and Hayes, B. J. and Brutman, J. N. and Valdmanis, P. N. and Bird, T. D. and Raskind, W. H. and Korvatska, O.},
title = {{TREM2 variants that cause early dementia and increase Alzheimer's disease risk affect gene splicing}},
journal = {Brain},
year = {2024}
}
Built from the record alzhub holds for this paper, not looked up. This record has no DOI, so the citation leaves it out. Volume, issue and page numbers are not held in the record. The record names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- The D134G TREM2 variant works mainly by causing skipping of exon 3, mimicking a splice-site mutation
- V126G and K186N variants cause splicing disruptions in addition to their known protein-level effects
- R62H and T96K — the most common Alzheimer's risk variants in European and African-ancestry populations, respectively — both increase abnormal exon 2 skipping
- Brain tissue from three independent cohorts confirmed a 1.8-fold increase in exon 2 skipping in R62H carriers
Why it matters
Several TREM2 variants, including the common Alzheimer's risk variants R62H and T96K, disrupt how the gene's RNA is spliced, not just the protein itself. This is a molecular genetics finding about how these risk variants work, not a treatment or prevention result.
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Study details
- Effect size1.8-fold increase in exon 2 skipping in R62H carriers vs. non-carriers
- Evidence strengthModerate
Limitations
Sample sizes for the brain-tissue splicing validation are not given as a single overall N; this is a mechanistic molecular study, not a clinical outcome study.
How this study scored 45/100
Published in a leading specialty journal. Scored zero for study design, sample size, studied in people, randomised / blinded and indexed in PubMed because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 28 of the 62 points we could judge it on, which is 45 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 4 / 5 | 2024 — within 3 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 | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 | 0 / 6 | No other study in this library cites it |
| 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 | 0 / 2 | No PubMed ID and no DOI — scores zero (not stated in the record — scored 0) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 28 / 62 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 28 of the 62 points we could judge it on is 45 out of 100. |
| Total | 45 / 100 | — |
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