title: Common DNA methylation alterations of Alzheimer's disease and aging in peripheral whole blood.
abstract: Alzheimer's disease (AD) is a common aging-related neurodegenerative illness. Recently, many studies have tried to identify AD- or aging-related DNA methylation (DNAm) biomarkers from peripheral whole blood (PWB). However, the origin of PWB biomarkers is still controversial. In this study, by analyzing 2565 DNAm profiles for PWB and brain tissue, we showed that aging-related DNAm CpGs (Age-CpGs) and AD-related DNAm CpGs (AD-CpGs) observable in PWB both mainly reflected DNAm alterations intrinsic in leukocyte subtypes rather than methylation differences introduced by the increased ratio of myeloid to lymphoid cells during aging or AD progression. The PWB Age-CpGs and AD-CpGs significantly overlapped 107 sites (P-value = 2.61×10-12) and 97 had significantly concordant methylation alterations in AD and aging (P-value < 2.2×10-16), which were significantly enriched in nervous system development, neuron differentiation and neurogenesis. More than 60.8% of these 97 concordant sites were found to be significantly correlated with age in normal peripheral CD4+ T cells and CD14+ monocytes as well as in four brain regions, and 44 sites were also significantly differentially methylated in different regions of AD brain tissue. Taken together, the PWB DNAm alterations related to both aging and AD could be exploited for identification of AD biomarkers.
authors.affiliation: Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Department of Bioinformatics, Fujian Medical University, Fuzhou, China.
authors.forename: Hongdong
authors.initials: H
authors.lastname: Li
authors.affiliation: Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Department of Bioinformatics, Fujian Medical University, Fuzhou, China.|College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Department of Bioinformatics, Fujian Medical University, Fuzhou, China.|Department of Preventive Medicine, School of Basic Medicine Sciences, Gannan Medical University, Ganzhou, China.
authors.forename: You
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Department of Bioinformatics, Fujian Medical University, Fuzhou, China.
authors.forename: Mengyao
authors.initials: M
authors.lastname: Li
authors.affiliation: Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Department of Bioinformatics, Fujian Medical University, Fuzhou, China.
authors.forename: Haidan
authors.initials: H
authors.lastname: Yan
authors.affiliation: Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Department of Bioinformatics, Fujian Medical University, Fuzhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Chenguang
authors.initials: C
authors.lastname: Wang
authors.affiliation: Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Department of Bioinformatics, Fujian Medical University, Fuzhou, China.
authors.forename: Guini
authors.initials: G
authors.lastname: Hong
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood / Q000235:genetics*; D000544:Alzheimer Disease / Q000097:blood / Q000235:genetics*; D001665:Binding Sites / Q000235:genetics; D001921:Brain / Q000378:metabolism / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D009154:Mutation; D055815:Young Adult
chemical_list: D018950:Lipopolysaccharide Receptors
keywords: Alzheimer’s disease; DNA methylation; Gerotarget; aging; peripheral whole blood