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Neurofilament-labeled pyramidal neurons and astrocytes are deficient in DNA methylation marks in Alzheimer's disease


Phipps, AJ and Vickers, JC and Taberlay, PC and Woodhouse, A, Neurofilament-labeled pyramidal neurons and astrocytes are deficient in DNA methylation marks in Alzheimer's disease, Neurobiology of Aging, 45 pp. 30-42. ISSN 0197-4580 (2016) [Refereed Article]

Copyright Statement

Copyright 2016 Elsevier Inc.

DOI: doi:10.1016/j.neurobiolaging.2016.05.003


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.

Item Details

Item Type:Refereed Article
Keywords:5-Hydroxymethylcytosine (5hmC), 5-Methylcytosine (5mC), Alzheimer's disease, DNA methylation, epigenetics, pyramidal neurons
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Neurosciences not elsewhere classified
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Phipps, AJ (Dr Andrew Phipps)
UTAS Author:Vickers, JC (Professor James Vickers)
UTAS Author:Taberlay, PC (Associate Professor Phillippa Taberlay)
UTAS Author:Woodhouse, A (Dr Adele Woodhouse)
ID Code:111489
Year Published:2016
Web of Science® Times Cited:18
Deposited By:Wicking Dementia Research and Education Centre
Deposited On:2016-09-15
Last Modified:2017-11-06

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