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Defining early changes in Alzheimer's disease from RNA sequencing of brain regions differentially affected by pathology
Guennewig B, Lim J, Marshall L, McCorkindale AN, Paasila PJ, Patrick E, Kril JJ, Halliday GM et al.. Scientific reports, 2021-03-01
Topic: Amyloid, tau and blood-test diagnosis
Plain-language summary
Tau pathology in Alzheimer's disease (AD) spreads in a predictable pattern that corresponds with disease symptoms and severity. At post-mortem there are cortical regions that range from mildly to severely affected by tau pathology and neuronal loss. A comparison of the molecular signatures of these differentially affected areas within cases and between cases and controls may allow the temporal modelling of disease progression. Here we used RNA sequencing to explore differential gene expression in the mildly affected primary visual cortex and moderately affected precuneus of ten age-, gender- and RNA quality-matched post-mortem brains from AD patients and healthy controls. The two regions in AD cases had similar transcriptomic signatures but there were broader abnormalities in the precuneus consistent with the greater tau load. Both regions were characterised by upregulation of immune-related genes such as those encoding triggering receptor expressed on myeloid cells 2 and membrane spanning 4-domains A6A and milder changes in insulin/IGF1 signalling. The precuneus in AD was also characterised by changes in vesicle secretion and downregulation of the interneuronal subtype marker, somatostatin. The 'early' AD transcriptome is characterised by perturbations in synaptic vesicle secretion on a background of neuroimmune dysfunction. In particular, the synaptic deficits that characterise AD may begin with the somatostatin division of inhibitory neurotransmission.
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APA 7th
Guennewig, B., Lim, J., Marshall, L., McCorkindale, A. N., Paasila, P. J., Patrick, E., et al. (2021). Defining early changes in Alzheimer's disease from RNA sequencing of brain regions differentially affected by pathology. Scientific reports. https://doi.org/10.1038/s41598-021-83872-z
Vancouver
Guennewig B, Lim J, Marshall L, McCorkindale AN, Paasila PJ, Patrick E, et al. Defining early changes in Alzheimer's disease from RNA sequencing of brain regions differentially affected by pathology. Scientific reports. 2021. doi:10.1038/s41598-021-83872-z. PMID: 33649380.
BibTeX
@article{guennewig2021-33649380,
author = {Guennewig, B. and Lim, J. and Marshall, L. and McCorkindale, A. N. and Paasila, P. J. and Patrick, E. and Kril, J. J. and Halliday, G. M. and others},
title = {{Defining early changes in Alzheimer's disease from RNA sequencing of brain regions differentially affected by pathology}},
journal = {Scientific reports},
year = {2021},
doi = {10.1038/s41598-021-83872-z},
pmid = {33649380},
url = {https://doi.org/10.1038/s41598-021-83872-z}
}
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Key findings
- The two regions in AD cases had similar transcriptomic signatures but there were broader abnormalities in the precuneus consistent with the greater tau load.
- Both regions were characterised by upregulation of immune-related genes such as those encoding triggering receptor expressed on myeloid cells 2 and membrane spanning 4-domains A6A and milder changes in insulin/IGF1 signalling.
- The precuneus in AD was also characterised by changes in vesicle secretion and downregulation of the interneuronal subtype marker, somatostatin.
- The 'early' AD transcriptome is characterised by perturbations in synaptic vesicle secretion on a background of neuroimmune dysfunction.
- In particular, the synaptic deficits that characterise AD may begin with the somatostatin division of inhibitory neurotransmission.
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Study details
- Evidence strengthLow
How this study scored 43/100
Published in a peer-reviewed 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 and multicenter collaboration, so those were left out: it earned 25 of the 58 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Scientific reports) |
| 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 33649380) |
| Free to read | 2 / 2 | Free to read |
| Points | 25 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 25 of the 58 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
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