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45/100

✓ Peer-reviewed alzhub usefulness score 45 out of 100. TREM2 and immune genetics

Topic: Inflammation, microglia and astrocytes

Plain-language summary

Variants in the triggering receptor expressed on myeloid cells 2 gene are linked with an increased risk of dementia, in particular the R47Hhet triggering receptor expressed on myeloid cells 2 variant is linked to late-onset Alzheimer's disease. Using human induced pluripotent stem cells-derived microglia, we assessed whether variations in the dynamics of exosome secretion, including their components, from these cells might underlie some of this risk. We found exosome size was not altered between common variant controls and R47Hhet variants, but the amount and constitution of exosomes secreted were different. Exosome quantities were rescued by incubation with an ATP donor or with lipids via a phosphatidylserine triggering receptor expressed on myeloid cells 2 ligand. Following a lipopolysaccharide or phagocytic cell stimulus, exosomes from common variant and R47Hhet microglia were found to contain cytokines, chemokines, APOE and triggering receptor expressed on myeloid cells 2. Differences were observed in the expression of CCL22, IL-1β and triggering receptor expressed on myeloid cells 2 between common variant and R47Hhet derived exosomes. Furthermore unlike common variant-derived exosomes, R47Hhet exosomes contained additional proteins linked to negative regulation of transcription and metabolic processes. Subsequent addition of exosomes to stressed neurones showed R47Hhet-derived exosomes to be less protective. These data have ramifications for the responses of microglia in Alzheimer's disease and may point to further targets for therapeutic intervention.

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APA 7th

Mallach, A., Gobom, J., Zetterberg, H., Hardy, J., Piers, T. M., Wray, S., et al. (2021). The influence of the R47H triggering receptor expressed on myeloid cells 2 variant on microglial exosome profiles. Brain communications. https://doi.org/10.1093/braincomms/fcab009

Vancouver

Mallach A, Gobom J, Zetterberg H, Hardy J, Piers TM, Wray S, et al. The influence of the R47H triggering receptor expressed on myeloid cells 2 variant on microglial exosome profiles. Brain communications. 2021. doi:10.1093/braincomms/fcab009. PMID: 34704019.

BibTeX

@article{mallach2021-34704019,
  author  = {Mallach, Anna and Gobom, Johan and Zetterberg, Henrik and Hardy, John and Piers, Thomas M and Wray, Selina and Pocock, Jennifer M},
  title   = {{The influence of the R47H triggering receptor expressed on myeloid cells 2 variant on microglial exosome profiles}},
  journal = {Brain communications},
  year    = {2021},
  doi     = {10.1093/braincomms/fcab009},
  pmid    = {34704019},
  url     = {https://doi.org/10.1093/braincomms/fcab009}
}

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How to read this study

Design: our record does not state a study design, so check the methods section of the original before weighing the result.
Size: the record gives no participant count. Look for one in the original before trusting a pattern.
Effect: the record gives no effect size, so the summary above cannot say how large any difference was.

What the evidence grade means here

This page is graded low. alzhub.org assigns the grade automatically from keywords in the abstract, not from reading the paper. Low means the abstract matched neither pattern. It is the default label, and it does not mean the work is poor; many sound lab and imaging papers land here. It can add at most 5 of the 100 points in the study score, and it is a label about design, not a verdict on whether the findings are true.

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Key findings

Variants in the triggering receptor expressed on myeloid cells 2 gene are linked with an increased risk of dementia, in particular the R47Hhet triggering receptor expressed on myeloid cells 2 variant is linked to late-onset Alzheimer's disease.
We found exosome size was not altered between common variant controls and R47Hhet variants, but the amount and constitution of exosomes secreted were different.

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Study details

Evidence strengthLow

How this study scored 45/100

Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded 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, cited by studies here, still being cited, senior author's track record, institution's track record, multicenter collaboration and free to read, so those were left out: it earned 25 of the 56 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 communications)
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	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	2021 — 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)
Randomized / blinded	0 / 2	No randomization 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
Multicenter collaboration	— / 3	Institutions not listed — left out of this score
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 34704019)
Free to read	— / 2	Access not recorded — left out of this score
Points	25 / 56	Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 25 of the 56 points we could judge it on is 45 out of 100.
Total	45 / 100	—

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