Epigenetic dysregulation of brainstem nuclei in the pathogenesis of Alzheimer's disease: looking in the correct place at the right time?

A. Iatrou, G. Kenis, B. P. F. Rutten, K. Lunnon, D. L. A. van den Hove*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

6 Citations (Web of Science)

Abstract

Even though the etiology of Alzheimer's disease (AD) remains unknown, it is suggested that an interplay among genetic, epigenetic and environmental factors is involved. An increasing body of evidence pinpoints that dysregulation in the epigenetic machinery plays a role in AD. Recent developments in genomic technologies have allowed for high throughput interrogation of the epigenome, and epigenome-wide association studies have already identified unique epigenetic signatures for AD in the cortex. Considerable evidence suggests that early dysregulation in the brainstem, more specifically in the raphe nuclei and the locus coeruleus, accounts for the most incipient, non-cognitive symptomatology, indicating a potential causal relationship with the pathogenesis of AD. Here we review the advancements in epigenomic technologies and their application to the AD research field, particularly with relevance to the brainstem. In this respect, we propose the assessment of epigenetic signatures in the brainstem as the cornerstone of interrogating causality in AD. Understanding how epigenetic dysregulation in the brainstem contributes to AD susceptibility could be of pivotal importance for understanding the etiology of the disease and for the development of novel diagnostic and therapeutic strategies.

Original languageEnglish
Pages (from-to)509-523
Number of pages15
JournalCellular and Molecular Life Sciences
Volume74
Issue number3
DOIs
Publication statusPublished - Feb 2017

Keywords

  • Alzheimer's disease
  • Locus coeruleus
  • Raphe nuclei
  • Epigenetics
  • DNA methylation
  • DNA hydroxymethylation
  • MILD COGNITIVE IMPAIRMENT
  • GENOME-WIDE ASSOCIATION
  • DORSAL RAPHE NUCLEUS
  • AMYLOID PRECURSOR PROTEIN
  • BETA-HYDROXYLASE ACTIVITY
  • GLOBAL DNA METHYLATION
  • LOCUS-COERULEUS
  • SENILE-DEMENTIA
  • NEURODEGENERATIVE DISEASES
  • NEUROFIBRILLARY TANGLES

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