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Dementia with Lewy bodies has a unique genetic profile, distinct from those of Alzheimer鈥檚 disease or Parkinson鈥檚 disease, according to the first large-scale genetic study of this common type of dementia which was led by 香港六合彩中特网 Institute of Neurology.

The genome-wide association study, conducted by a 香港六合彩中特网-led collaboration of 65 academics in 11 countries and funded by Alzheimer鈥檚 Society and the Lewy Body Society, is published today in The Lancet Neurology.

鈥淒ementia with Lewy bodies accounts for 10-15% of dementia cases, yet our understanding of it lags beyond the more well-known Alzheimer鈥檚 disease, partly because it鈥檚 commonly misdiagnosed. Our findings clarify the disease鈥檚 distinctive genetic signature, which should, in the future, help improve clinical trials, and lead to more targeted treatments,鈥� said the study鈥檚 lead author, Dr Jose Bras (香港六合彩中特网 Institute of Neurology).

The research team genotyped 1,743 patients with dementia with Lewy bodies (DLB) 鈥� including both clinical samples and 1,324 pathological samples assessed post-mortem 鈥� 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鈥檚 and Parkinson鈥檚, respectively. Another one of the loci identified, SNCA, is also associated with Parkinson鈥檚, but differently 鈥� 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鈥檚 and Parkinson鈥檚 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鈥檚. The heritability was particularly high for four specific chromosomes, suggesting that further research could focus on those chromosomes to identify novel loci.

鈥淎s the gene loci that had previously been associated with DLB were also implicated in Alzheimer鈥檚 and Parkinson鈥檚, it was unclear if DLB鈥檚 genetic roots were simply a combination of the other two diseases. We鈥檝e 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鈥� explained the study鈥檚 first author, Dr Rita Guerreiro (香港六合彩中特网 Institute of Neurology).

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.

鈥淒LB and Parkinson鈥檚 have many similarities, as people with DLB often develop Parkinson鈥檚 symptoms, and Parkinson鈥檚 often leads to dementia. By understanding the genetic underpinnings, we can more effectively target treatments to the different groups,鈥� said Dr Bras.

鈥淒ementia with Lewy bodies is often misunderstood as being a mixture of Alzheimer鈥檚 and Parkinson鈥檚, but this confirms it鈥檚 actually a unique condition. Despite DLB being one of the most common forms of dementia in older people, until now there simply hasn鈥檛 been enough information on its causes, so the finding that up to 36% of cases might be genetically inherited is a real revelation. As the largest and most detailed study of its kind, these results will be invaluable in future research, and it鈥檚 a great milestone on the road towards our goal of understanding and treating all forms of dementia.鈥� Dr Doug Brown, Director of Research at Alzheimer鈥檚 Society who funded the study

Further information

• Guerreiro et al.. Lancet Neurology, Volume 17, No. 1, p64鈥�74. Available online 18 December 2017. DOI: 10.1016/S1474-4422(17)30400-3