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The epigenetic landscape of Alzheimer's disease

Nature Neuroscience volume 17, pages 1138–1140 (2014)Cite this article

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Two independent epigenome-wide association studies of Alzheimer's disease cohorts have identified overlapping methylation signals in four loci, ANK1, RPL13, RHBDF2 and CDH23, not previously associated with Alzheimer's disease. These studies also suggest that epigenetic changes contribute more to Alzheimer's disease than expected.

Alzheimer's disease is a devastating condition, currently without an effective cure, treatment or prevention, that robs people of their memories and abilities. With an estimated 26 million people living with the condition worldwide, a figure that is expected to rise as populations age, it is one of the most burdensome threats to public health today1. Despite this, and despite growing public attention and funding being directed into dementia research, the fundamental cause of Alzheimer's disease remains elusive. Although recent large, collaborative genome-wide association studies (GWAS) have been successful in identifying numerous genes associated with the condition2, the variants and mechanisms underlying these associations are generally unclear. In addition, the proportion of the genetic heritability explained by common variants is only 3–4% for each locus. Thus, it has proposed that other types of genetic variation, such as low-frequency and rare variants or epigenetic changes, may help to explain the condition3. In this issue of Nature Neuroscience, Lunnon et al.4 and De Jager et al.5 present the results of the first two large-scale, epigenome-wide association studies (EWAS) in Alzheimer's disease, with results being replicated in independent cohorts. Their results showcase one of the latest tools for dissecting the etiology of complex disorders and give new insights into the basis of Alzheimer's disease.

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Figure 1: Loci showing methylation changes with replicable effect in the two independent studies.

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Authors and Affiliations

  1. Jenny Lord and Carlos Cruchaga are in the Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.,

    Jenny Lord & Carlos Cruchaga

  2. Carlos Cruchaga is in the Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University School of Medicine, St. Louis, Missouri, USA.,

    Carlos Cruchaga

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  1. Jenny Lord
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Correspondence to Carlos Cruchaga.

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Lord, J., Cruchaga, C. The epigenetic landscape of Alzheimer's disease. Nat Neurosci 17, 1138–1140 (2014). https://doi.org/10.1038/nn.3792

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