Evidence map›Paper›PMID 30045751›Full record

ArticleEpigenetics & chromatin2018

DNA methylation analysis on purified neurons and glia dissects age and Alzheimer's disease-specific changes in the human cortex.

Gilles Gasparoni, Sebastian Bultmann, Pavlo Lutsik, Theo F J Kraus, Sabrina Sordon, Julia Vlcek, Vanessa Dietinger, Martina Steinmaurer, Melanie Haider, Christopher B Mulholland and 7 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Epigenetics & chromatin, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers, 11 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
142citing papers in PubMed, 11 pooled it
12.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

142 citing papers in PubMed, 11 syntheses or guidelines pooled it, 253 citations in OpenAlex.

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82 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 4 institutions in 1 country.

Gilles GasparoniDepartment of Genetics, University of Saarland (UdS), Campus, 66123, Saarbrücken, Germany.ORCID http://orcid.org/0000-0002-6423-4637
Sebastian BultmannDepartment of Biology and Center for Integrated Protein Science, Ludwig-Maximilians-University (LMU), 82152, Munich, Germany.
Pavlo LutsikEpigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
Theo F J KrausCenter for Neuropathology and Prion Research, Ludwig-Maximilians-University (LMU), 82152, Munich, Germany.
Sabrina SordonDepartment of Psychiatry and Psychotherapy, Saarland University Hospital (UKS), 66424, Homburg, Germany.
Julia VlcekCenter for Neuropathology and Prion Research, Ludwig-Maximilians-University (LMU), 82152, Munich, Germany.
Vanessa DietingerCenter for Neuropathology and Prion Research, Ludwig-Maximilians-University (LMU), 82152, Munich, Germany.
Martina SteinmaurerCenter for Neuropathology and Prion Research, Ludwig-Maximilians-University (LMU), 82152, Munich, Germany.
Melanie HaiderCenter for Neuropathology and Prion Research, Ludwig-Maximilians-University (LMU), 82152, Munich, Germany.
Christopher B MulhollandDepartment of Biology and Center for Integrated Protein Science, Ludwig-Maximilians-University (LMU), 82152, Munich, Germany.
Thomas ArzbergerCenter for Neuropathology and Prion Research, Ludwig-Maximilians-University (LMU), 82152, Munich, Germany.
Sigrun RoeberCenter for Neuropathology and Prion Research, Ludwig-Maximilians-University (LMU), 82152, Munich, Germany.
Matthias RiemenschneiderDepartment of Psychiatry and Psychotherapy, Saarland University Hospital (UKS), 66424, Homburg, Germany.
Hans A KretzschmarCenter for Neuropathology and Prion Research, Ludwig-Maximilians-University (LMU), 82152, Munich, Germany.
Armin GieseCenter for Neuropathology and Prion Research, Ludwig-Maximilians-University (LMU), 82152, Munich, Germany.
Heinrich LeonhardtDepartment of Biology and Center for Integrated Protein Science, Ludwig-Maximilians-University (LMU), 82152, Munich, Germany.
Jörn WalterDepartment of Genetics, University of Saarland (UdS), Campus, 66123, Saarbrücken, Germany. j.walter@mx.uni-saarland.de.
Ludwig-Maximilians-Universität München · DESaarland University · DECenter for Integrated Protein Science Munich · DEGerman Cancer Research Center · DE

Funding

Bundesministerium für Bildung und Forschung 01KU1216FDeutsche Forschungsgemeinschaft SFB 1064 A17/22
6 · The paper itself

Abstract

backgroundEpigenome-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.

resultsWe 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.

conclusionsOur 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.

Indexed as

DNA MethylationADAM17 ProteinAgingAlzheimer DiseaseAmyloid beta-Protein PrecursorAutopsyCell SeparationEpigenesis, GeneticEpigenomicsGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansNeurogliaNeuronsOrgan SpecificityTranscriptomeADAM17 ProteinADAM17 protein, humanAmyloid beta-Protein PrecursorAPP protein, humanAgingAlzheimer’s diseaseBrainCell sortingDNA methylationEpigeneticsEWASGliaNeurodegenerationNeuron

Identifiers

PMID30045751
PMCPMC6058387
OpenAlexW2884329485

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.