title: Differential DNA Methylation of MicroRNA Genes in Temporal Cortex from Alzheimer's Disease Individuals.
abstract: This study investigated for the first time the genomewide DNA methylation changes of noncoding RNA genes in the temporal cortex samples from individuals with Alzheimer's disease (AD). The methylome of 10 AD individuals and 10 age-matched controls were obtained using Illumina 450 K methylation array. A total of 2,095 among the 15,258 interrogated noncoding RNA CpG sites presented differential methylation, 161 of which were associated with miRNA genes. In particular, 10 miRNA CpG sites that were found to be hypermethylated in AD compared to control brains represent transcripts that have been previously associated with the disease. This miRNA set is predicted to target 33 coding genes from the neuregulin receptor complex (ErbB) signaling pathway, which is required for the neurons myelination process. For 6 of these miRNA genes (MIR9-1, MIR9-3, MIR181C, MIR124-1, MIR146B, and MIR451), the hypermethylation pattern is in agreement with previous results from literature that shows downregulation of miR-9, miR-181c, miR-124, miR-146b, and miR-451 in the AD brain. Our data implicate dysregulation of miRNA methylation as contributor to the pathogenesis of AD.
authors.affiliation: Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, Rua do Matão 277, 05508-090 São Paulo, SP, Brazil.
authors.forename: Darine
authors.initials: D
authors.lastname: Villela
authors.affiliation: International Research Center, CIPE, AC Camargo Hospital, Rua Taguá 440, 01508-010 São Paulo, SP, Brazil.
authors.forename: Rodrigo F
authors.initials: RF
authors.lastname: Ramalho
authors.affiliation: International Research Center, CIPE, AC Camargo Hospital, Rua Taguá 440, 01508-010 São Paulo, SP, Brazil.
authors.forename: Aderbal R T
authors.initials: AR
authors.lastname: Silva
authors.affiliation: Institute and Department of Psychiatry, University of São Paulo Medical School, Avenida Doutor Arnaldo 455, 01246-000 São Paulo, SP, Brazil.
authors.forename: Helena
authors.initials: H
authors.lastname: Brentani
authors.affiliation: Discipline of Geriatrics, Department of Internal Medicine, University of São Paulo Medical School, Avenida Doutor Arnaldo 455, 01246-000 São Paulo, SP, Brazil; Brazilian Aging Brain Study Group, LIM22, Department of Pathology, University of São Paulo Medical School, Avenida Doutor Arnaldo 455, 01246-000 São Paulo, SP, Brazil.
authors.forename: Claudia K
authors.initials: CK
authors.lastname: Suemoto
authors.affiliation: Brazilian Aging Brain Study Group, LIM22, Department of Pathology, University of São Paulo Medical School, Avenida Doutor Arnaldo 455, 01246-000 São Paulo, SP, Brazil; Department of Pathology, University of São Paulo Medical School, Avenida Doutor Arnaldo 455, 01246-000 São Paulo, SP, Brazil.
authors.forename: Carlos Augusto
authors.initials: CA
authors.lastname: Pasqualucci
authors.affiliation: Brazilian Aging Brain Study Group, LIM22, Department of Pathology, University of São Paulo Medical School, Avenida Doutor Arnaldo 455, 01246-000 São Paulo, SP, Brazil; Memory and Aging Center, Department of Neurology, University of California, 675 Nelson Rising Lane, P.O. Box 1207, San Francisco, CA 94143, USA.
authors.forename: Lea T
authors.initials: LT
authors.lastname: Grinberg
authors.affiliation: Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, Rua do Matão 277, 05508-090 São Paulo, SP, Brazil.
authors.forename: Ana C V
authors.initials: AC
authors.lastname: Krepischi
authors.affiliation: Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, Rua do Matão 277, 05508-090 São Paulo, SP, Brazil.
authors.forename: Carla
authors.initials: C
authors.lastname: Rosenberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D013702:Temporal Lobe / Q000378:metabolism* / Q000473:pathology
chemical_list: D035683:MicroRNAs