The Genetics of Dementia with Lewy Bodies: Current Understanding and Future Directions

Curr Neurol Neurosci Rep. 2018 Aug 10;18(10):67. doi: 10.1007/s11910-018-0874-y.

Abstract

Purpose of review: Dementia with Lewy bodies (DLB) is a neurodegenerative disease that can be clinically and pathologically similar to Parkinson's disease (PD) and Alzheimer's disease (AD). Current understanding of DLB genetics is insufficient and has been limited by sample size and difficulty in diagnosis. The first genome-wide association study (GWAS) in DLB was performed in 2017; a time at which the post-GWAS era has been reached in many diseases.

Recent findings: DLB shares risk loci with AD, in the APOE E4 allele, and with PD, in variation at GBA and SNCA. Interestingly, the GWAS suggested that DLB may also have genetic risk factors that are distinct from those in AD and PD. Although off to a slow start, recent studies have reinvigorated the field of DLB genetics and these results enable us to start to have a more complete understanding of the genetic architecture of this disease.

Keywords: DLB; Dementia with Lewy bodies; GWAS; Genetics; Next-generation sequencing.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease
  • C9orf72 Protein
  • Carrier Proteins
  • Genome-Wide Association Study
  • Group VI Phospholipases A2
  • Humans
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Lewy Bodies
  • Lewy Body Disease / complications
  • Lewy Body Disease / diagnosis*
  • Lewy Body Disease / genetics*
  • Lysosomal Membrane Proteins
  • Membrane Glycoproteins
  • Molecular Chaperones
  • Parkinson Disease
  • Receptors, Immunologic
  • Receptors, Scavenger

Substances

  • C9orf72 Protein
  • C9orf72 protein, human
  • Carrier Proteins
  • DNAJC13 protein, human
  • GIGYF2 protein, human
  • Lysosomal Membrane Proteins
  • Membrane Glycoproteins
  • Molecular Chaperones
  • Receptors, Immunologic
  • Receptors, Scavenger
  • SCARB2 protein, human
  • TREM2 protein, human
  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Group VI Phospholipases A2
  • PLA2G6 protein, human