Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Feb;74(3):509-523.
doi: 10.1007/s00018-016-2361-4. Epub 2016 Sep 14.

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

A Iatrou  1 , G Kenis  1 , B P F Rutten  1 , K Lunnon  2 , D L A van den Hove  3   4
Affiliations
Review

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

A Iatrou et al. Cell Mol Life Sci. 2017 Feb.

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.

Keywords: Alzheimer’s disease; DNA hydroxymethylation; DNA methylation; Epigenetics; Locus coeruleus; Raphe nuclei.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflict of interest.

References

    1. Guo JU, Su Y, Shin JH, Shin J, Li H, Xie B, Zhong C, Hu S, Le T, Fan G, Zhu H, Chang Q, Gao Y, Ming GL, Song H. Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain. Nat Neurosci. 2014;17(2):215–222. doi: 10.1038/nn.3607. - DOI - PMC - PubMed
    1. Selkoe DJ. Preventing Alzheimer’s disease. Science. 2012;337(6101):1488–1492. doi: 10.1126/science.1228541. - DOI - PubMed
    1. Braak H, Thal DR, Ghebremedhin E, Del Tredici K. Stages of the pathologic process in alzheimer disease: age categories from 1 to 100 years. J Neuropathol Exp Neurol. 2011;70(11):960–969. doi: 10.1097/NEN.0b013e318232a379. - DOI - PubMed
    1. Elobeid A, Soininen H, Alafuzoff I. Hyperphosphorylated tau in young and middle-aged subjects. Acta Neuropathol. 2012;123(1):97–104. doi: 10.1007/s00401-011-0906-z. - DOI - PMC - PubMed
    1. Mann DA, Hardy J. Amyloid or tau: the chicken or the egg? Acta Neuropathol. 2013;126(4):609–613. doi: 10.1007/s00401-013-1162-1. - DOI - PubMed

Publication types

LinkOut - more resources