Elucidating novel dysfunctional pathways in Alzheimer's disease by integrating loci identified in genetic and epigenetic studies
(c) 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
© 2016 The Authors.Alzheimer's disease is a complex neurodegenerative disorder. A large number of genome-wide association studies have been performed, which have been supplemented more recently by the first epigenome-wide association studies, leading to the identification of a number of novel loci altered in disease. Twin studies have shown monozygotic twin discordance for Alzheimer's disease (Gatz et al., 2006), leading to the conclusion that a combination of genetic and epigenetic mechanisms is likely to be involved in disease etiology (Lunnon & Mill, 2013). This review focuses on identifying overlapping pathways between published genome-wide association studies and epigenome-wide association studies, highlighting dysfunctional synaptic, lipid metabolism, plasma membrane/cytoskeleton, mitochondrial, and immune cell activation pathways. Identifying common pathways altered in genetic and epigenetic studies will aid our understanding of disease mechanisms and identify potential novel targets for pharmacological intervention.
This work was funded by a grant from Bristol Research into Alzheimer's and Care of the Elderly and the Alzheimer's Society (grant AS-PG-14-038) to KL.
This is the author accepted manuscript. The final version is freely available from Elsevier via the DOI in this record.
Vol. 6, June 2016, pp. 32 - 50