Multiscale network modeling of oligodendrocytes reveals molecular components of myelin dysregulation in Alzheimer's disease
McKenzie AT, Moyon S, Wang M, Katsyv I, Song WM, Zhou X, Dammer EB, Duong DM et al.. Molecular neurodegeneration, 2017-11-06
Topic: Brain proteins, microglia and lab models
Background Oligodendrocytes (OLs) and myelin are critical for normal brain function and have been implicated in neurodegeneration. Several lines of evidence including neuroimaging and neuropathological data suggest that Alzheimer's disease (AD) may be associated with dysmyelination and a breakdown of OL-axon communication. Methods In order to understand this phenomenon on a molecular level, we systematically interrogated OL-enriched gene networks constructed from large-scale genomic, transcriptomic and proteomic data obtained from human AD postmortem brain samples. We then validated these networks using gene expression datasets generated from mice with ablation of major gene expression nodes identified in our AD-dysregulated networks. Results The robust OL gene coexpression networks that we identified were highly enriched for genes associated with AD risk variants, such as BIN1 and demonstrated strong dysregulation in AD. We further corroborated the structure of the corresponding gene causal networks using datasets generated from the brain of mice with ablation of key network drivers, such as UGT8, CNP and PLP1, which were identified from human AD brain data. Further, we found that mice with genetic ablations of Cnp mimicked aspects of myelin and mitochondrial gene expression dysregulation seen in brain samples from patients with AD, including decreased protein expression of BIN1 and GOT2. Conclusions This study provides a molecular blueprint of the dysregulation of gene expression networks of OL in AD and identifies key OL- and myelination-related genes and networks that are highly associated with AD.
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APA 7th
McKenzie, A. T., Moyon, S., Wang, M., Katsyv, I., Song, W. M., Zhou, X., et al. (2017). Multiscale network modeling of oligodendrocytes reveals molecular components of myelin dysregulation in Alzheimer's disease. Molecular neurodegeneration. https://doi.org/10.1186/s13024-017-0219-3
Vancouver
McKenzie AT, Moyon S, Wang M, Katsyv I, Song WM, Zhou X, et al. Multiscale network modeling of oligodendrocytes reveals molecular components of myelin dysregulation in Alzheimer's disease. Molecular neurodegeneration. 2017. doi:10.1186/s13024-017-0219-3. PMID: 29110684.
BibTeX
@article{mckenzie2017-29110684,
author = {McKenzie, A. T. and Moyon, S. and Wang, M. and Katsyv, I. and Song, W. M. and Zhou, X. and Dammer, E. B. and Duong, D. M. and others},
title = {{Multiscale network modeling of oligodendrocytes reveals molecular components of myelin dysregulation in Alzheimer's disease}},
journal = {Molecular neurodegeneration},
year = {2017},
doi = {10.1186/s13024-017-0219-3},
pmid = {29110684},
url = {https://doi.org/10.1186/s13024-017-0219-3}
}
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Key findings
- Several lines of evidence including neuroimaging and neuropathological data suggest that Alzheimer's disease (AD) may be associated with dysmyelination and a breakdown of OL-axon communication.
- Results The robust OL gene coexpression networks that we identified were highly enriched for genes associated with AD risk variants, such as BIN1 and demonstrated strong dysregulation in AD.
- Further, we found that mice with genetic ablations of Cnp mimicked aspects of myelin and mitochondrial gene expression dysregulation seen in brain samples from patients with AD, including decreased protein expression of BIN1 and GOT2.
- Conclusions This study provides a molecular blueprint of the dysregulation of gene expression networks of OL in AD and identifies key OL- and myelination-related genes and networks that are highly associated with AD.
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Study details
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / 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 multi-centre collaboration, so those were left out: it earned 24 of the 58 points we could judge it on, which is 41 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Molecular neurodegeneration) |
| 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 | 2 / 5 | 2017 — 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 | — / 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 |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 29110684) |
| Free to read | 2 / 2 | Free to read |
| Points | 24 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 24 of the 58 points we could judge it on is 41 out of 100. |
| Total | 41 / 100 | — |
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