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

Lookup NU author(s): Dr Claire Troakes, Professor Raj Kalaria

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Abstract

© 2018 Elsevier Inc. 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.


Publication metadata

Author(s): Smith AR, Smith RG, Burrage J, Troakes C, Al-Sarraj S, Kalaria RN, Sloan C, Robinson AC, Mill J, Lunnon K

Publication type: Article

Publication status: Published

Journal: Neurobiology of Aging

Year: 2019

Volume: 74

Pages: 70-76

Print publication date: 01/02/2019

Online publication date: 13/10/2018

Acceptance date: 18/09/2018

ISSN (print): 0197-4580

ISSN (electronic): 1558-1497

Publisher: Elsevier Inc.

URL: https://doi.org/10.1016/j.neurobiolaging.2018.09.024

DOI: 10.1016/j.neurobiolaging.2018.09.024


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