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Researchers Discover Genetic Profile Unique to Dementia With Lewy Bodies

Allison Inserro
In a discovery that could potentially pave the way for more targeted treatments, researchers announced that dementia with Lewy bodies (DLB) has a unique genetic profile, separate from those of Alzheimer disease or Parkinson disease (PD). Researchers also found that DLB has heritability traits similar to PD.
In a discovery that could potentially pave the way for more targeted treatments, researchers announced that dementia with Lewy bodies (DLB) has a unique genetic profile, separate from those of Alzheimer disease (AD) or Parkinson disease (PD).

It is the first large-scale genetic study of this common type of dementia. Researchers also found that DLB has heritability traits similar to PD.

The genome-wide association study was conducted by a collaboration led by University College London (UCL), with 65 academics in 11 countries. Results were published December 15 in The Lancet Neurology.

"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,” said the study's lead author, Dr Jose Bras, UCL Institute of Neurology and Alzheimer's Society senior research fellow, in a statement. “Our findings clarify the disease's distinctive genetic signature, which should, in the future, help improve clinical trials, and lead to more targeted treatments."

Researchers genotyped 1743 patients with dementia with Lewy bodies (DLB)—including both clinical samples and 1324 pathological samples assessed post-mortem—and 4454 controls. They found that:
  • 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 AD and PD, respectively.
  • Another one of the loci identified, SNCA, is also associated with PD, but differently: the researchers found that a different part of the gene is linked to DLB.
  • There was preliminary evidence for a gene locus that had not been previously associated with DLB, but the results did not reach significance.
  • A few loci that are associated with AD and PD do not appear to be associated with DLB.
For the first time, researchers were able to identify a heritability estimate of DLB, 36%, which is similar to that of PD. The heritability was particularly high for 4 specific chromosomes, suggesting that further research could focus on those chromosomes to identify novel loci.

"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," explained the study's first author, Dr Rita Guerreiro, UCL Institute of Neurology and Alzheimer's Society senior research fellow.

"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," she said.

"Despite DLB being one of the most common forms of dementia in older people, until now there simply hasn't been enough information on its causes, so the finding that up to 36% of cases might be genetically inherited is a real revelation,” said Dr Doug Brown, research director at the Alzheimer's Society, which funded the study. The Lewy Body Society also provided funding.

 
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