DNA methylation and Alzheimer's disease



  • © Springer Science+Business Media, LLC 2010. All rights reserved. Epigenetics plays a direct and indirect role in the chances of developing Alzheimer's disease. The decreased DNA methylation status with increasing age of the amyloid precursor protein (APP) gene promoter will boost transcription of this gene, leading to higher levels of APP. Furthermore, both the BACE and PS1 genes show similar decreased promoter methylation with aging, causing higher levels - and activity - of β- and γ-secretases, increasing APP processing toward Aβ production. Together, this increases the levels of Aβ that will lead to the development of the pathology that is characteristic of sporadic AD. Furthermore, epigenetics plays a role through the nutritional status of the individual, i.e., through low folate and high homocysteine levels the DNA methylation level can be decreased. It is of interest to note that it has been shown that AD patients tend to have low levels of folate and high levels of homocysteine. Finally, parental influences in the inheritance of AD have been demonstrated, likely caused by gene imprinting.
  • Digital Object Identifier (doi)

    International Standard Book Number (isbn) 13

  • 9781441906380
  • Start Page

  • 315
  • End Page

  • 326