DNA methylation analysis on purified neurons and glia dissects age and Alzheimer's disease-specific changes in the human cortex
Gasparoni G, Bultmann S, Lutsik P, Kraus TFJ, Sordon S, Vlcek J, Dietinger V, Steinmaurer M et al.. Epigenetics & chromatin, 2018-07-25
Topic: Brain proteins, microglia and lab models
Background Epigenome-wide association studies (EWAS) based on human brain samples allow a deep and direct understanding of epigenetic dysregulation in Alzheimer's disease (AD). However, strong variation of cell-type proportions across brain tissue samples represents a significant source of data noise. Here, we report the first EWAS based on sorted neuronal and non-neuronal (mostly glia) nuclei from postmortem human brain tissues. Results We show that cell sorting strongly enhances the robust detection of disease-related DNA methylation changes even in a relatively small cohort. We identify numerous genes with cell-type-specific methylation signatures and document differential methylation dynamics associated with aging specifically in neurons such as CLU, SYNJ2 and NCOR2 or in glia RAI1,CXXC5 and INPP5A. Further, we found neuron or glia-specific associations with AD Braak stage progression at genes such as MCF2L, ANK1, MAP2, LRRC8B, STK32C and S100B. A comparison of our study with previous tissue-based EWAS validates multiple AD-associated DNA methylation signals and additionally specifies their origin to neuron, e.g., HOXA3 or glia (ANK1). In a meta-analysis, we reveal two novel previously unrecognized methylation changes at the key AD risk genes APP and ADAM17. Conclusions Our data highlight the complex interplay between disease, age and cell-type-specific methylation changes in AD risk genes thus offering new perspectives for the validation and interpretation of large EWAS results.
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APA 7th
Gasparoni, G., Bultmann, S., Lutsik, P., Kraus, T. F. J., Sordon, S., Vlcek, J., et al. (2018). DNA methylation analysis on purified neurons and glia dissects age and Alzheimer's disease-specific changes in the human cortex. Epigenetics & chromatin. https://doi.org/10.1186/s13072-018-0211-3
Vancouver
Gasparoni G, Bultmann S, Lutsik P, Kraus TFJ, Sordon S, Vlcek J, et al. DNA methylation analysis on purified neurons and glia dissects age and Alzheimer's disease-specific changes in the human cortex. Epigenetics & chromatin. 2018. doi:10.1186/s13072-018-0211-3. PMID: 30045751.
BibTeX
@article{gasparoni2018-30045751,
author = {Gasparoni, G. and Bultmann, S. and Lutsik, P. and Kraus, T. F. J. and Sordon, S. and Vlcek, J. and Dietinger, V. and Steinmaurer, M. and others},
title = {{DNA methylation analysis on purified neurons and glia dissects age and Alzheimer's disease-specific changes in the human cortex}},
journal = {Epigenetics \& chromatin},
year = {2018},
doi = {10.1186/s13072-018-0211-3},
pmid = {30045751},
url = {https://doi.org/10.1186/s13072-018-0211-3}
}
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Key findings
- However, strong variation of cell-type proportions across brain tissue samples represents a significant source of data noise.
- Results We show that cell sorting strongly enhances the robust detection of disease-related DNA methylation changes even in a relatively small cohort.
- We identify numerous genes with cell-type-specific methylation signatures and document differential methylation dynamics associated with aging specifically in neurons such as CLU, SYNJ2 and NCOR2 or in glia RAI1,CXXC5 and INPP5A.
- Further, we found neuron or glia-specific associations with AD Braak stage progression at genes such as MCF2L, ANK1, MAP2, LRRC8B, STK32C and S100B.
- Conclusions Our data highlight the complex interplay between disease, age and cell-type-specific methylation changes in AD risk genes thus offering new perspectives for the validation and interpretation of large EWAS results.
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Study details
- Study designmeta-analysis
- Evidence strengthHigh
How this study scored 69/100
Published in a peer-reviewed journal, and it is a meta-analysis pooling many studies. Scored zero for sample size, effect reported and studied in people 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 40 of the 58 points we could judge it on, which is 69 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Epigenetics & chromatin) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 12 / 12 | A meta-analysis pooling many studies |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2018 — 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 | A review of other studies — randomisation is not credited here |
| 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 30045751) |
| Free to read | 2 / 2 | Free to read |
| Points | 40 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 40 of the 58 points we could judge it on is 69 out of 100. |
| Total | 69 / 100 | — |
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