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

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 current study, we used bisulfite pyrosequencing to quantify DNA methylation across eight CpG sites within a 118bp 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, whilst in donors with Vascular dementia and Dementia with Lewy bodies we observed elevated ANK1 DNA methylation only in individuals with co-existing 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 suggests that ANK1 is characterized by region and disease-specific differential DNA methylation in multiple neurodegenerative diseases.