Редактирование: SYNJ2 (раздел)

==Publications==

{{medline-entry
|title=DNA methylation analysis on purified neurons and glia dissects age and Alzheimer's disease-specific changes in the human cortex.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30045751
|abstract=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. 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]]. 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.
|mesh-terms=* ADAM17 Protein
* Aging
* Alzheimer Disease
* Amyloid beta-Protein Precursor
* Autopsy
* Cell Separation
* DNA Methylation
* Epigenesis, Genetic
* Epigenomics
* Genetic Predisposition to Disease
* Genome-Wide Association Study
* Humans
* Neuroglia
* Neurons
* Organ Specificity
* Transcriptome
|keywords=* Aging
* Alzheimer’s disease
* Brain
* Cell sorting
* DNA methylation
* EWAS
* Epigenetics
* Glia
* Neurodegeneration
* Neuron
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6058387
}}