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Neurofilament-labeled pyramidal neurons and astrocytes are deficient in DNA methylation marks in Alzheimer's disease
journal contribution
posted on 2023-05-18, 22:24 authored by Andrew PhippsAndrew Phipps, James VickersJames Vickers, Phillippa TaberlayPhillippa Taberlay, Adele WoodhouseAdele WoodhouseThere 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.
History
Publication title
Neurobiology of AgingVolume
45Pagination
30-42ISSN
0197-4580Department/School
Wicking Dementia Research Education CentrePublisher
Elsevier Science IncPlace of publication
United StatesRights statement
Copyright 2016 Elsevier Inc.Repository Status
- Restricted