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Age-related Disturbances in DNA (hydroxy)methylation in APP/PS1 Mice

Leonidas Chouliaras1,2, Roy Lardenoije1, Gunter Kenis1

  • 1School for Mental Health and Neuroscience (MHeNS), Department of Psychiatry and Neuropsychology, Faculty of Health, Medicine and Life Sciences, European Graduate School of Neuroscience (EURON), Maastricht University Medical Centre, Maastricht, The Netherlands.

Translational Neuroscience
|February 13, 2019
PubMed

Insights

Brain aging affects DNA methylation patterns. Alzheimer's disease (AD) models show altered DNA methylation and hydroxymethylation in the hippocampus, impacting brain aging and AD progression.

Area of Science:

  • Neuroscience
  • Epigenetics
  • Molecular Biology

Background:

  • Brain aging is linked to abnormal DNA methylation.
  • Alzheimer's disease (AD) brains show altered DNA methylation markers.
  • DNA hydroxymethylation's role in aging and AD is understudied.

Purpose of the Study:

  • Investigate age-related changes in DNA methylation (5-mC) and hydroxymethylation (5-hmC) in the hippocampus.
  • Compare these changes in APPswe/PS1ΔE9 transgenic mice (AD model) and wild-type mice.
  • Determine the impact of amyloid processing on hippocampal epigenetics during aging.

Main Methods:

  • Utilized quantitative immunohistochemistry to analyze 5-mC and 5-hmC levels.
  • Examined 3- and 9-month-old mice (both transgenic and wild-type).
  • Focused analysis on three distinct hippocampal sub-regions.

Main Results:

  • Wild-type mice exhibited age-related increases in both 5-mC and 5-hmC.
  • APPswe/PS1ΔE9 mice showed decreased 5-mC at 9 months.
  • No significant age-related changes in 5-hmC were observed in APPswe/PS1ΔE9 mice.

Conclusions:

  • Aberrant amyloid processing influences DNA methylation and hydroxymethylation balance in the aging mouse hippocampus.
  • These epigenetic alterations may contribute to AD pathogenesis.
  • Further research is needed to elucidate the precise mechanisms linking amyloid pathology and epigenetic dysregulation in AD.
Keywords:
APPswe/PS1ΔE9AgingAlzheimer’s DiseaseDNA hy-droxymethylationDNA methylationEpigenetics

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