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

  title={The Genetics of Dementia with Lewy Bodies: Current Understanding and Future Directions},
  author={Tatiana Orme and Rita Guerreiro and Jose T Bras},
  journal={Current Neurology and Neuroscience Reports},
Purpose of ReviewDementia 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 FindingsDLB shares risk loci with AD, in… 

Family History is Associated with Phenotype in Dementia with Lewy Bodies

It is suggested that genetic factors are important in DLB and that the identification of new genetic factors will probably improve the prediction of prognosis.

Genetic Architecture and Molecular, Imaging and Prodromic Markers in Dementia with Lewy Bodies: State of the Art, Opportunities and Challenges

The up-to-now reported knowledge on the genetic architecture of DLB is summarized and the use of prodromal biomarkers as well as recent promising candidates from alternative body fluids and new imaging techniques are discussed.

Dementia with Lewy bodies: an update and outlook

Basic concepts and definitions of dementia with Lewy bodies are presented, based on the current understanding, that should guide the community to address open questions that will lead to improved diagnosis and novel therapeutic strategies for DLB and other synucleinopathies.

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In this review, a detailed review of epigenetic modifications identified for LBD in human cells, postmortem, and peripheral tissues is provided, and the current achievements and directions for future research are shown.

Diagnosis of Dementia with Lewy Bodies: Fluctuations, Biomarkers, and beyond

Advances and remaining challenges in the diagnosis of DLB are discussed, including a review of the current consensus criteria for DLB, and particular consideration is given to advancements in quantification of cognitive fluctuations through improved clinical instruments, EEG, and other advanced biomarkers.

The Nosology of Lewy Body Disorders From Analytic–Epidemiologic and Statistical Vantage Points

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Clinical Update on C9orf72: Frontotemporal Dementia, Amyotrophic Lateral Sclerosis, and Beyond.

This chapter will address all issues and summarize the recent updates about clinical aspects of C9orf72 disease, focusing on both the common and the less typical phenotypes.



An update on the genetics of dementia with Lewy bodies.

Genetic analysis implicates APOE, SNCA and suggests lysosomal dysfunction in the etiology of dementia with Lewy bodies

It is indicated that DLB has a unique genetic risk profile when compared with the two most common neurodegenerative diseases and that the lysosome may play an important role in the etiology of this disorder.

A novel locus for dementia with Lewy bodies: a clinically and genetically heterogeneous disorder.

The data re-emphasize the genetic heterogeneity of DLB, and strongly support the existence of a gene for familial DLB on 2q35-q36, which will be the first novel causal gene for DLB and can be expected to open new avenues for biological studies of the disease process.

TREM2 p.R47H substitution is not associated with dementia with Lewy bodies

It is suggested that dementia with Lewy bodies may be a distinct disease with shared genetic risk factors with PD and AD and variants at both the α-synuclein (SNCA) and APOE loci as influencing the individual risk.

High Frequency of GBA Gene Mutations in Dementia With Lewy Bodies Among Ashkenazi Jews.

One in 3 AJ patients diagnosed with DLB were carriers of a GBA mutation, making it the most common genetic mutation identified in association with this disease and with any dementia disorder.

GBA mutations increase risk for Lewy body disease with and without Alzheimer disease pathology

GBA is a susceptibility gene across the LBD spectrum, but not in AD, and appears to convey a higher risk for PD and pDLB than for LBD-AD, which might be more similar to one another in genetic determinants and pathophysiology than either disease is to either disease.