Distinct Genetic Profile In Dementia With Lewy Bodies

Dementia with Lewy bodies has a unique genetic profile, different from those seen in Alzheimer’s disease or Parkinson’s disease, according to the first genome-wide association study of this common type of dementia.

The study was conducted by a University College London-led collaboration of 65 academics in 11 countries.

“Dementia with Lewy bodies accounts for 10-15% of dementia cases, yet our understanding of it lags beyond the more well-known Alzheimer’s disease, partly because it’s commonly misdiagnosed. Our findings clarify the disease’s distinctive genetic signature, which should, in the future, help improve clinical trials, and lead to more targeted treatments,”

said the study’s lead author, Dr Jose Bras, UCL Institute of Neurology and Alzheimer’s Society senior research fellow.

Dementia With Lewy Bodies

The research team genotyped 1,743 patients with dementia with Lewy bodies (DLB) – including both clinical samples and 1,324 pathological samples assessed post-mortem – and 4,454 controls.

Two of the genetic loci that were found to be significantly associated with DLB, APOE and GBA, bore the same associations to DLB as they do to Alzheimer’s and Parkinson’s, respectively. Another one of the loci identified, SNCA, is also associated with Parkinson’s, but differently – the researchers found that a different part of the gene is linked to DLB.

They also found preliminary evidence for a gene locus that had not been previously associated with DLB, but the results did not reach significance.

The team also found that a few loci that are associated with Alzheimer’s and Parkinson’s do not appear to be associated with DLB.

The researchers were able to identify a heritability estimate of DLB for the first time, at 36%, which is similar to that of Parkinson’s. The heritability was particularly high for four specific chromosomes, suggesting that further research could focus on those chromosomes to identify novel loci.

Unique Genetic Profile

The study’s first author, Dr Rita Guerreiro, explained:

“As the gene loci that had previously been associated with DLB were also implicated in Alzheimer’s and Parkinson’s, it was unclear if DLB’s genetic roots were simply a combination of the other two diseases. We’ve confirmed that instead, it has its own unique genetic profile. The selection of study participants has been a substantial challenge in dementia trials. Our findings can be used to identify more clearly which type of dementia each person has, so that they can take part in the right clinical trial, which could lead to better treatments and diagnostic tools.”

Guerreiro is a UCL Institute of Neurology and Alzheimer’s Society senior research fellow.

The researchers also hope that by advancing the understanding of which genes play a role in DLB, their results will aid in the development of targeted therapies.

“DLB and Parkinson’s have many similarities, as people with DLB often develop Parkinson’s symptoms, and Parkinson’s often leads to dementia. By understanding the genetic underpinnings, we can more effectively target treatments to the different groups,”

said Dr Bras. Funding for the work came from The Alzheimer’s Society and the Lewy Body Society.

Guerreiro, Rita et al.
Investigating the genetic architecture of dementia with Lewy bodies: a two-stage genome-wide association study
The Lancet Neurology , Volume 17 , Issue 1 , 64 – 74

Image: Kate Patterson, CC BY-ND