title: Neurofilament-labeled pyramidal neurons and astrocytes are deficient in DNA methylation marks in Alzheimer's disease.
abstract: There is increasing evidence that epigenetic alterations may play a role in Alzheimer's disease (AD); yet, there is little information regarding epigenetic modifications in specific cell types. We assessed DNA methylation (5-methylcytosine [5mC]) and hydroxymethylation (5-hydroxymethylcytosine [5hmC]) marks specifically in neuronal and glial cell types in the inferior temporal gyrus of human AD cases and age-matched controls. Interestingly, neurofilament (NF)-labeled pyramidal neurons that are vulnerable to AD pathology are deficient in extranuclear 5mC in AD cases compared with controls. We also found that fewer astrocytes exhibited nuclear 5mC and 5hmC marks in AD cases compared with controls. However, there were no alterations in 5mC and 5hmC in disease-resistant calretinin interneurons or microglia in AD, and there was no alteration in the density of 5mC- or 5hmC-labeled nuclei in near-plaque versus plaque-free regions in late-AD cases. 5mC and 5hmC were present in a high proportion of neurofibrillary tangles, suggesting no loss of DNA methylation marks in tangle bearing neurons. We provide evidence that epigenetic dysregulation may be occurring in astrocytes and NF-positive pyramidal neurons in AD.
authors.affiliation: Wicking Dementia Research and Education Centre, University of Tasmania, Hobart, Tasmania, Australia.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Phipps
authors.affiliation: Wicking Dementia Research and Education Centre, University of Tasmania, Hobart, Tasmania, Australia.
authors.forename: James C
authors.initials: JC
authors.lastname: Vickers
authors.affiliation: Chromatin Dynamics Group, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia; St Vincent's Clinical School, Faculty of Medicine, University of New South Wales Australia, Sydney, New South Wales, Australia.
authors.forename: Phillippa C
authors.initials: PC
authors.lastname: Taberlay
authors.affiliation: Wicking Dementia Research and Education Centre, University of Tasmania, Hobart, Tasmania, Australia. Electronic address: Adele.Woodhouse@utas.edu.au.
authors.forename: Adele
authors.initials: A
authors.lastname: Woodhouse
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives* / Q000032:analysis*; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D001253:Astrocytes / Q000473:pathology*; D015415:Biomarkers / Q000032:analysis; D019175:DNA Methylation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007382:Intermediate Filaments / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000378:metabolism; D017966:Pyramidal Cells / Q000473:pathology*
chemical_list: D015415:Biomarkers; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine
keywords: 5-Hydroxymethylcytosine (5hmC); 5-Methylcytosine (5mC); Alzheimer's disease; DNA methylation; Epigenetics; Pyramidal neurons