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Neurobiol Aging. 2019 Feb;74:70-76. doi: 10.1016/j.neurobiolaging.2018.09.024. Epub 2018 Oct 13.

A cross-brain regions study of ANK1 DNA methylation in different neurodegenerative diseases.

Author information

1
University of Exeter Medical School, University of Bristol, Exeter, UK.
2
Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, UK.
3
Institute of Neuroscience, Newcastle University, Newcastle, UK.
4
Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
5
Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
6
University of Exeter Medical School, University of Bristol, Exeter, UK. Electronic address: k.lunnon@exeter.ac.uk.

Abstract

Recent epigenome-wide association studies in Alzheimer's disease have highlighted consistent robust neuropathology-associated DNA hypermethylation of the ankyrin 1 (ANK1) gene in the cortex. The extent to which altered ANK1 DNA methylation is also associated with other neurodegenerative diseases is not currently known. In the present study, we used bisulfite pyrosequencing to quantify DNA methylation across 8 CpG sites within a 118 bp region of the ANK1 gene across multiple brain regions in Alzheimer's disease, Vascular dementia, Dementia with Lewy bodies, Huntington's disease, and Parkinson's disease. We demonstrate disease-associated ANK1 hypermethylation in the entorhinal cortex in Alzheimer's disease, Huntington's disease, and Parkinson's disease, whereas in donors with Vascular dementia and Dementia with Lewy bodies, we observed elevated ANK1 DNA methylation only in individuals with coexisting Alzheimer's disease pathology. We did not observe any disease-associated differential ANK1 DNA methylation in the striatum in Huntington's disease or the substantia nigra in Parkinson's disease. Our data suggest that ANK1 is characterized by region and disease-specific differential DNA methylation in multiple neurodegenerative diseases.

KEYWORDS:

Alzheimer's disease (AD); Ankyrin 1 (ANK1); Brain; DNA methylation (5-methylcytosine – 5 mC); Dementia with Lewy bodies (DLB); Epigenetics; Huntington's disease (HD); Parkinson's disease (PD); Vascular dementia (VaD)

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