Epigenetic changes in Alzheimer's disease: Decrements in DNA methylation

Diego Mastroeni, Andrew Grover, Elaine Delvaux, Charisse Whiteside, Paul Coleman, Joseph Rogers

Research output: Contribution to journalArticle

201 Citations (Scopus)

Abstract

DNA methylation is a vital component of the epigenetic machinery that orchestrates changes in multiple genes and helps regulate gene expression in all known vertebrates. We evaluated immunoreactivity for two markers of DNA methylation and eight methylation maintenance factors in entorhinal cortex layer II, a region exhibiting substantial Alzheimer's disease (AD) pathology in which expression changes have been reported for a wide variety of genes. We show, for the first time, neuronal immunoreactivity for all 10 of the epigenetic markers and factors, with highly significant decrements in AD cases. These decrements were particularly marked in PHF1/PS396 immunoreactive, neurofibrillary tangle-bearing neurons. In addition, two of the DNA methylation maintenance factors, DNMT1 and MBD2, have been reported also to interact with ribosomal RNAs and ribosome synthesis. Consistent with these findings, DNMT1 and MBD2, as well as p66α, exhibited punctate cytoplasmic immunoreactivity that co-localized with the ribosome markers RPL26 and 5.8. s rRNA in ND neurons. By contrast, AD neurons generally lacked such staining, and there was a qualitative decrease in RPL26 and 5.8. s rRNA immunoreactivity. Collectively, these findings suggest epigenetic dysfunction in AD-vulnerable neurons.

Original languageEnglish (US)
Pages (from-to)2025-2037
Number of pages13
JournalNeurobiology of Aging
Volume31
Issue number12
DOIs
StatePublished - Dec 1 2010
Externally publishedYes

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DNA Methylation
Epigenomics
Alzheimer Disease
Neurons
Ribosomes
Maintenance
Entorhinal Cortex
Neurofibrillary Tangles
Ribosomal RNA
Methylation
Genes
Vertebrates
Pathology
Staining and Labeling
Gene Expression

Keywords

  • Alzheimer's disease
  • DNA methylation
  • Epigenetics
  • Neuron
  • Ribosome

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology
  • Clinical Neurology

Cite this

Epigenetic changes in Alzheimer's disease : Decrements in DNA methylation. / Mastroeni, Diego; Grover, Andrew; Delvaux, Elaine; Whiteside, Charisse; Coleman, Paul; Rogers, Joseph.

In: Neurobiology of Aging, Vol. 31, No. 12, 01.12.2010, p. 2025-2037.

Research output: Contribution to journalArticle

Mastroeni, Diego ; Grover, Andrew ; Delvaux, Elaine ; Whiteside, Charisse ; Coleman, Paul ; Rogers, Joseph. / Epigenetic changes in Alzheimer's disease : Decrements in DNA methylation. In: Neurobiology of Aging. 2010 ; Vol. 31, No. 12. pp. 2025-2037.
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