GSE66351 DNA methylation profiling of neuron and glia for the dissection of cell type, age and Alzheimer ’s disease-specific changes in the human brain

Contributors : Gilles Gasparoni ; Sebastian Bultmann ; Pavlo Lutsik ; Theo Kraus ; Julia Vlcek ; Vanessa Dietinger ; Martina Steinmaurer ; Matthias Riemenschneider ; Hans A Kretzschmar ; Armin Giehse ; Heinrich Leonhardt ; J örn WalterSeries Type : Methylation profiling by arrayOrganism : Homo sapiensAlzheimer ’s disease (AD) is a progressive brain disorder caused by altered neuronal and glial cell functions. Illumina 450K profiling of cells (nuclei) sorted from post- mortem human brains allowed us assigning cell type- specific epigenetic changes to aging and AD progression. Among a few thousand cell ty pe-specific differentially methylated CpGs (DMCGs) changing with age we identify prominent clusters in the AD genes, CLU, SYNJ2, ANK1 and MCF2L. A distinct set of age independent AD-specific DMCGs shows strong cell specific changes in the genes TOLLIP, BACE2, PKAR1B, PDE9A, ROBO2, FERMT2, UGT8, SPON 1, INPP5D, LNFG and SRPK2. Some AD-specific DMCGs even reveal incremental changes with advancing BRAAK stages. In summary we observe a striking presence of DMCGs in major LOAD genes establishing novel connections between genetic and epigenetic contributions to AD. In addition the cell-specific assoc iation allows to functionally discriminate epigenetic effects of aging from those related to AD in the human brain.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Methylation profiling by array Homo sapiens Source Type: research