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

Adam R Smith; Rebecca G Smith; Joe Burrage; Claire Troakes; Safa Al-Sarraj; Rajesh N Kalaria; Carolyn Sloan; Andrew C Robinson; Jonathan Mill; Katie Lunnon

doi:10.1016/j.neurobiolaging.2018.09.024

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

Adam R Smith, Rebecca G Smith, Joe Burrage, Claire Troakes, Safa Al-Sarraj, Rajesh N Kalaria, Carolyn Sloan, Andrew C Robinson, Jonathan Mill, Katie Lunnon

Division of Neuroscience

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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.

Original language	English
Pages (from-to)	70-76
Number of pages	7
Journal	Neurobiology of Aging
Volume	74
Early online date	13 Oct 2018
DOIs	https://doi.org/10.1016/j.neurobiolaging.2018.09.024
Publication status	Published - Feb 2019

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10.1016/j.neurobiolaging.2018.09.024

Smith et al ANK1 Neurobiol Aging 2018 Accepted versionAccepted author manuscript, 261 KBLicence: CC BY-NC-ND

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title = "A cross-brain regions study of ANK1 DNA methylation in different neurodegenerative diseases",

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.",

author = "Smith, {Adam R} and Smith, {Rebecca G} and Joe Burrage and Claire Troakes and Safa Al-Sarraj and Kalaria, {Rajesh N} and Carolyn Sloan and Robinson, {Andrew C} and Jonathan Mill and Katie Lunnon",

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doi = "10.1016/j.neurobiolaging.2018.09.024",

language = "English",

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journal = "Neurobiology of Aging",

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T1 - A cross-brain regions study of ANK1 DNA methylation in different neurodegenerative diseases

AU - Smith, Adam R

AU - Smith, Rebecca G

AU - Burrage, Joe

AU - Troakes, Claire

AU - Al-Sarraj, Safa

AU - Kalaria, Rajesh N

AU - Sloan, Carolyn

AU - Robinson, Andrew C

AU - Mill, Jonathan

AU - Lunnon, Katie

PY - 2019/2

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N2 - 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.

AB - 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.

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DO - 10.1016/j.neurobiolaging.2018.09.024

M3 - Article

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SN - 0197-4580

VL - 74

SP - 70

EP - 76

JO - Neurobiology of Aging

JF - Neurobiology of Aging

ER -

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

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