Press release
Tuesday, February 16, 2021
The NIH-led study locates five genes that may play a critical role in Lewy body dementia.
In a study conducted by researchers at the National Institutes of Health, scientists found that five genes may play a critical role in determining whether a person will suffer from Lewy body dementia, a devastating disorder that creates the brain with clumps of abnormal deposits of proteins called Lewy bodies. Lewy bodies are also a hallmark of Parkinson’s disease. The results, published in Nature Genetics, not only supported the links between Parkinson’s disease, but also suggested that people with Lewy body dementia may have genetic profiles similar to those suffering from Alzheimer’s disease.
Lewy body dementia is a devastating brain disorder for which we do not have effective treatments. Patients often appear to suffer from the most severe of Alzheimer’s and Parkinson’s diseases. Our results support the idea that this may be due to the fact that Lewy body dementia is caused by a range of problems that can be seen in both disorders, “said Sonja Scholz, MD, Ph.D., investigator at the National Institute of Neurological Disorders. of NIH and Stroke (NINDS) and lead author of the study.We hope that these results will act as a model for understanding the disease and developing new treatments.
The study was led by Dr. Scholz’s team and researchers from the laboratory of Bryan J. Traynor, MD, Ph.D., principal investigator at the NIH’s National Institute on Aging.
Lewy body dementia usually affects people over the age of 65. Early signs of the disease include hallucinations, mood swings, and problems with thinking, movement, and sleep. Patients who initially have cognitive and behavioral problems are usually diagnosed as having dementia with Lewy bodies, but are sometimes misdiagnosed with Alzheimer’s disease. Alternatively, many patients, who are initially diagnosed with Parkinson’s disease, may eventually have difficulty thinking and disposing caused by Lewy body dementia. In both cases, as the disease worsens, patients become severely disabled and may die within eight years of diagnosis.
A growing body of evidence suggests that genetics may play a role in the disorder and that some cases can be inherited. Scientists have found that some of these rare cases can be caused by mutations in the alpha-synuclein gene (SNCA), the main protein found in Lewy bodies. Further studies have found that variants of the apolipoprotein E (APOE) gene, which are known to play a role in Alzheimer’s disease, may also play a role in Lewy body dementia.
“Compared to other neurodegenerative disorders, very little is known about the genetic forces behind Lewy body dementia,” said Dr. Traynor. “To get a better understanding, we wanted to study the genetic architecture of Lewy body dementia.”
To do this, they compared the chromosomal DNA sequences of 2,981 patients with dementia in Lewy’s body with those of 4,931 healthy, age-appropriate control participants. Samples were collected from participants with European ancestors at 44 sites: 17 in Europe and 27 in North America. DNA sequencing was led by Clifton Dalgard, PhD and researchers at The American Genome Center, a state-of-the-art laboratory at the University of Health Sciences Uniformed Services and supported by Henry M. Jackson. Foundation for the Development of Military Medicine.
Initially, they found that the sequences of five genes in patients with Lewy body dementia were often different from those in controls, suggesting that these genes may be important. It was the first time two of the genes, called BIN1 and TMEM175, had been implicated in the disease. These genes may also be linked to Alzheimer’s and Parkinson’s diseases. The other three genes, SNCA, APOE and GBA, have been implicated in previous studies and have therefore enhanced the importance of genes in Lewy body dementia.
The researchers also saw differences in the same five genes when they compared the DNA sequences of another 970 patients with dementia in Lewy’s body with a new set of 8,928 control subjects, confirming the initial results.
Further analysis suggested that changes in the activity of these genes may lead to dementia and that the GBA gene may have a particularly strong influence on the disease. The gene encodes instructions for beta-glucosylceramidase, a protein that helps a cell’s recycling system break down sugar fats. The researchers found that both common and rare variants in the GBA gene are linked to Lewy body dementia.
“These results provide a list of five genes that we strongly suspect play a role in Lewy body dementia,” said Dr. Traynor.
Finally, to examine the apparent links between Lewy body dementia and other neurodegenerative diseases, the researchers further analyzed data from previous studies on Alzheimer’s and Parkinson’s disease. They found that the genetic profiles of the patients in this study were more likely to suffer from either Alzheimer’s or Parkinson’s disease than the elderly control subjects. These predictions occurred even after reducing the potential impact of genes known to cause Alzheimer’s and Parkinson’s disease, such as APOE and SNCA. Interestingly, the patient’s genetic risk profiles for Alzheimer’s disease, on the one hand, or Parkinson’s disease, on the other, did not overlap.
Although Alzheimer’s and Parkinson’s disease are very different molecular and clinical disorders, our results support the idea that the problems that cause these diseases can also occur in Lewy body dementia, said Dr. Scholz. The challenge we face in treating these patients is to determine the specific problems that cause dementia. We hope that such studies will help physicians find precise treatments for each patient’s condition. ”
To help with this effort, the team published the genome sequence data from the study on the Genotypes and Phenotypes Database (dbGaP), a National Library of Medicine website where researchers can freely search for new perspectives on the causes of body dementia. Lewy and other disorders.
Article:
Chia, R., et al. Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides information on complex genetic architecture. Nature Genetics, February 15, 2021 DOI: 10.1038 / s41588-021-00785-3
This study was partially supported by NIH intramural research programs from the National Institute for Neurological Disorders and Stroke (NS003154) and the National Institute for Aging (AG000935).
NINDS (https://www.ninds.nih.gov) is the largest national funder of research on the brain and nervous system. The mission of NINDS is to seek basic knowledge about the brain and nervous system and to use this knowledge to reduce the burden of neurological diseases.
About the National Institute for Aging (ANI): ANI is leading the US federal government’s effort to conduct and support research on aging, health and well-being in the elderly. Visit the ANI website for information on a range of aging topics in English and Spanish. Learn more about age-related cognitive impairment and neurodegenerative diseases through its Alzheimer’s Center and Dementias Education and Referral (ADEAR) website. Stay connected with NIA!
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