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Adv Exp Med Biol. 2017;978:303-319. doi: 10.1007/978-3-319-53889-1_16.

DNA Modifications and Alzheimer's Disease.

Author information

1
University of Exeter Medical School, RILD, Barrack Road, Exeter, Devon, UK.
2
University of Exeter Medical School, RILD, Barrack Road, Exeter, Devon, UK. K.Lunnon@exeter.ac.uk.

Abstract

Alzheimer's disease (AD) is a complex neurodegenerative disease, affecting millions of people worldwide. While a number of studies have focused on identifying genetic variants that contribute to the development and progression of late-onset AD, the majority of these only have a relatively small effect size. There are also a number of other risk factors, for example, age, gender, and other comorbidities; however, how these influence disease risk is not known. Therefore, in recent years, research has begun to investigate epigenetic mechanisms for a potential role in disease etiology. In this chapter, we discuss the current state of play for research into DNA modifications in AD, the most well studied being 5-methylcytosine (5-mC). We describe the earlier studies of candidate genes and global measures of DNA modifications in human AD samples, in addition to studies in mouse models of AD. We focus on recent epigenome-wide association studies (EWAS) in human AD, using microarray technology, examining a number of key study design issues pertinent to such studies. Finally, we discuss how new technological advances could further progress the research field.

KEYWORDS:

5-hydroximethylcytosine; 5-methylcytosine; Alzheimer’s disease; EWAS

PMID:
28523553
DOI:
10.1007/978-3-319-53889-1_16
[Indexed for MEDLINE]

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