Published in
Nature Research, Nature Neuroscience, 9(17), p. 1164-1170, 2014
DOI: 10.1038/nn.3782
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- [www.ncbi.nlm.nih.gov] | PDF
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- [europepmc.org] | PDF
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Tools
Methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer's disease
,
Philip L. De Jager,
Gyan Srivastava,
Manuela Volta,
Claire Troakes ,
Safa Al-Sarraj,
Joe Burrage,
Ruby Macdonald,
Daniel Condliffe,
Lorna W. Harries,
Pavel Katsel,
Vahram Haroutunian,
Zachary Kaminsky
and other authors.
Full text: Download
Abstract
Alzheimer's disease (AD) is a chronic neurodegenerative disorder that is characterized by progressive neuropathology and cognitive decline. We performed a cross-tissue analysis of methylomic variation in AD using samples from four independent human post-mortem brain cohorts. We identified a differentially methylated region in the ankyrin 1 (ANK1) gene that was associated with neuropathology in the entorhinal cortex, a primary site of AD manifestation. This region was confirmed as being substantially hypermethylated in two other cortical regions (superior temporal gyrus and prefrontal cortex), but not in the cerebellum, a region largely protected from neurodegeneration in AD, or whole blood obtained pre-mortem from the same individuals. Neuropathology-associated ANK1 hypermethylation was subsequently confirmed in cortical samples from three independent brain cohorts. This study represents, to the best of our knowledge, the first epigenome-wide association study of AD employing a sequential replication design across multiple tissues and highlights the power of this approach for identifying methylomic variation associated with complex disease.