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Epigenetic regulation in the pathophysiology of Lewy body dementia

Lookup NU author(s): Professor Alan Thomas, Professor Patrick Chinnery, Professor John O'Brien

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Abstract

© 2020Lewy body dementia encompasses both dementia with Lewy bodies and Parkinson's disease dementia. Although both are common causes of dementia, they remain relatively understudied. The review summarises the clinico-pathologic characteristics of Lewy Body dementia and discusses the genetic and environmental evidence contributing to the risk of developing the condition. Considering that the pathophysiology of Lewy body dementia is not yet fully understood, here we focus on the role of epigenetic mechanisms as potential key mediators of gene–environment interactions in the development of the disease. We examine available important data on genomics, epigenomics, gene expression and proteomic studies in Lewy body dementia on human post-mortem brain and peripheral tissues. Genetic variation and epigenetic modifications in key genes involved in the disorder, such as apolipoprotein E (APOE), α-synuclein (SNCA) and glucocerobrosidase (GBA), suggest a central involvement of epigenetics in DLB but conclusive evidence is scarce. This is due to limitations of existing literature, such as small sample sizes, lack of replication and lack of studies interrogating cell-type specific epigenetic modifications in the brain. Future research in the field can improve the understanding of this common but complex and rapidly progressing type of dementia and potentially open early diagnostic and effective therapeutic targets.


Publication metadata

Author(s): Chouliaras L, Kumar GS, Thomas AJ, Lunnon K, Chinnery PF, O'Brien JT

Publication type: Review

Publication status: Published

Journal: Progress in Neurobiology

Year: 2020

Volume: 192

Print publication date: 01/09/2020

Online publication date: 12/05/2020

Acceptance date: 06/05/2020

ISSN (print): 0301-0082

ISSN (electronic): 1873-5118

Publisher: Elsevier Ltd

URL: https://doi.org/10.1016/j.pneurobio.2020.101822

DOI: 10.1016/j.pneurobio.2020.101822

PubMed id: 32407744


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