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Genetic variability in response to amyloid beta deposition influences Alzheimer's disease risk
Salih DA, Bayram S, Guelfi S, Reynolds RH, Shoai M, Ryten M, Brenton JW, Zhang D et al.. Brain communications, 2019-10-10
Topic: Amyloid, tau and blood-test diagnosis
Genome-wide association studies of late-onset Alzheimer's disease risk have previously identified genes primarily expressed in microglia that form a transcriptional network. Using transgenic mouse models of amyloid deposition, we previously showed that many of the mouse orthologues of these risk genes are co-expressed and associated with amyloid pathology. In this new study, we generate an improved RNA-seq-derived network that is expressed in amyloid-responsive mouse microglia and we statistically compare this with gene-level variation in previous human Alzheimer's disease genome-wide association studies to predict at least four new risk genes for the disease ( OAS1 , LAPTM5 , ITGAM/ CD11b and LILRB4 ).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Salih, D. A., Bayram, S., Guelfi, S., Reynolds, R. H., Shoai, M., Ryten, M., et al. (2019). Genetic variability in response to amyloid beta deposition influences Alzheimer's disease risk. Brain communications. https://doi.org/10.1093/braincomms/fcz022
Vancouver
Salih DA, Bayram S, Guelfi S, Reynolds RH, Shoai M, Ryten M, et al. Genetic variability in response to amyloid beta deposition influences Alzheimer's disease risk. Brain communications. 2019. doi:10.1093/braincomms/fcz022. PMID: 32274467.
BibTeX
@article{salih2019-32274467,
author = {Salih, D. A. and Bayram, S. and Guelfi, S. and Reynolds, R. H. and Shoai, M. and Ryten, M. and Brenton, J. W. and Zhang, D. and others},
title = {{Genetic variability in response to amyloid beta deposition influences Alzheimer's disease risk}},
journal = {Brain communications},
year = {2019},
doi = {10.1093/braincomms/fcz022},
pmid = {32274467},
url = {https://doi.org/10.1093/braincomms/fcz022}
}
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Key findings
- Using transgenic mouse models of amyloid deposition, we previously showed that many of the mouse orthologues of these risk genes are co-expressed and associated with amyloid pathology.
- In this new study, we generate an improved RNA-seq-derived network that is expressed in amyloid-responsive mouse microglia and we statistically compare this with gene-level variation in previous human Alzheimer's disease genome-wide association studies to predict at least four new risk genes for the disease ( OAS1 , LAPTM5 , ITGAM/ CD11b and LILRB4 ).
- Of the mouse orthologues of these genes Oas1a is likely to respond directly to amyloid at the transcriptional level, similarly to established risk gene Trem2 , because the increase in Oas1a and Trem2 transcripts in response to amyloid deposition in transgenic mice is significantly higher than both the increase of the average microglial transcript and the increase in microglial number.
- In contrast, the mouse orthologues of LAPTM5 , ITGAM /CD11b and LILRB4 ( Laptm5 , Itgam /CD11b and Lilra5 ) show increased transcripts in the presence of amyloid plaques similar in magnitude to the increase of the average microglial transcript and the increase in microglia number, except that Laptm5 and Lilra5 transcripts increase significantly quicker than the average microglial transcript as the plaque load becomes dense.
Why it matters
Using mouse models of amyloid deposition, this study predicted at least four new risk genes for Alzheimer's disease by comparing a microglial network with human genetic data. It is a genetic prediction study and does not test any treatment or prevention.
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Study details
- Evidence strengthLow
How this study scored 49/100
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 (Brain communications) |
| Journal's citation record | 0 / 4 | Brain Communications: journal h-index 67 (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 | 2 / 5 | 2019 — within 10 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 111 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 12.3 citations a year over 9 year(s) since 2019 |
| Impact for its field and year | 3 / 6 | Cited 7.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 7 other studies in this library |
| Still being cited | 2 / 4 | Cited 44 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author John Hardy: h-index 205 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 32274467) |
| Free to read | 2 / 2 | Free to read |
| Total | 49 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1093/braincomms/fcz022
- PubMed: 32274467
- Original source →
- Free full text: Brain Communications →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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