Press release
Tuesday, February 16, 2021
An NIH-led study finds five genes that may play a critical role in Lewy body depression.
In a study led by researchers from the National Institutes of Health, scientists found that five genes could play a crucial role in determining whether a person suffers from Lewy body depression, a destructive disorder which irritates the brain with clumps of superficial protein deposits called Lewy bodies. Lewy bodies are also a sign of Parkinson’s disease. The findings, published in Nature Genetics, not only supported the link of the disease to Parkinson’s disease but also suggested that people with Lewy body dementia may have genetic profiles similar to those with the disease. Sharing Alzheimer’s.
“Lewy body depression is a terrible brain disorder for which we do not have effective treatments. Patients often suffer from the most severe of Alzheimer’s and Parkinson’s diseases. Our results support the notion that this may be due to Lewy body depression caused by a spectrum of disorders seen in both disorders, ”said Sonja Scholz, MD, Ph.D. D., a researcher at the NIH National Institute of Neurological Disorders and Stroke (NINDS) and lead author of the study. “We hope that these results will be a plan for understanding the disease and developing new treatments. ”
The study was led by Dr. Scholz’s team and researchers in the laboratory of Bryan J. Traynor, MD, Ph.D., senior researcher at the NIH National Institute on Aging (NIA).
Lewy body depression usually affects people over 65 years of age. Early signs of the disease include hallucinations, mood swings, and problems with thinking, movements, and sleep. Patients with mental and behavioral problems are usually initially diagnosed with dementia with Lewy bodies, but are sometimes mistakenly diagnosed with Alzheimer’s disease. On the other hand, many patients, initially diagnosed with Parkinson’s disease, may have problems with thinking and feeling caused by Lewy body depression. In all cases, as the disease progresses, 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 may be inherited. Scientists have discovered that some of these rare cases can be caused by mutations in the gene for alpha-synuclein (SNCA), the main protein found in Lewy bodies. Further studies have found that changes in the gene for apolipoprotein E (APOE), which are known to play a role in Alzheimer’s disease, may play a role in Lewy body depression.
“Compared to other neurodegenerative disorders, there is very little information about the genetic forces behind Lewy body depression,” said Dr. Traynor. “To gain a better understanding we wanted to study the genetic architecture of Lewy body depression.”
To do this, they compared the DNA chromosomal sequences of 2,981 Lewy body dementia patients with those of 4,931 healthy control participants, by age. Samples were collected from European ancestry partners at 44 sites: 17 in Europe and 27 across North America. The DNA series was led by Clifton Dalgard, Ph.D., and researchers at The American Genome Center, a series of state-of-the-art laboratories at the University of Health Sciences Clothing Services with support from the Henry M. Jackson Foundation for Advancement weapon medicine.
First, they found that the sequences of five genes from Lewy body dementia patients were often different from the controls, suggesting that these genes may be important. This was the first time that two of the genes, known as BIN1 and TMEM175, had been involved in the disease. These genes may be linked to Alzheimer’s and Parkinson’s diseases. The other three genes, SNCA, APOE, and GBA, had been involved in previous studies, thus reinforcing the importance of the genes in Lewy body depression.
The researchers also observed differences in the same five genes when they compared the DNA sequences of another 970 Lewy body dementia patients with a new set of 8,928 control subjects, confirming their initial results.
Further analysis suggested that changes in the activity of these genes may lead to depression and that the GBA gene may have a strong effect on the disease. The gene encodes instructions for beta-glucosylceramidase, a protein that helps a cell’s recycling system break down sugar fat. The researchers found that both common and rare mutations in the GBA gene are linked to Lewy body depression.
“These results provide a list of five genes that we strongly believe are involved in Lewy body depression,” said Dr. Traynor.
Finally, to examine the similar links between Lewy body depression and other neurodegenerative diseases, the researchers further analyzed data from previous studies of Alzheimer’s and Parkinson’s disease. They found that the patients in this study had higher genetic imaging with higher chances of suffering from Alzheimer’s disease or Parkinson’s than the age-controlled subjects. These predictions were held even after the potential impact of known Alzheimer’s and Parkinson’s genes, such as APOE and SNCA, was downplayed. Interestingly, the patient’s genetic risk profiles for Alzheimer’s disease, on the one hand, or Parkinson’s disease, on the other, were not consistent.
“Although Alzheimer’s disease and Parkinson’s disorder are clinically very different, our results support the view that the complications caused by these diseases may occur in Lewy body depression,” said Dr. Scholz. “The challenge for us in treating these patients is to identify the specific problems that cause depression. We hope that studies like this will help doctors find the right treatments for each patient’s condition. ”
To help with this effort, the team published the genome sequence data from the study of the Genotypes and Phenotypes (dbGaP) database, the National Library of Medicine’s website where researchers can freely search for new perspectives on the causes of Lewy body depression and other. disorders.
Article:
Chia, R., et al. Genome sequencing analysis identifies new loci associated with Lewy body depression and provides us with an insight into the complex genetic architecture. Nature Genetics, February 15, 2021 DOI: 10.1038 / s41588-021-00785-3
This study was supported in part by the NIH Intramural Research Programs at the National Institute of Neurological Disorders and Stroke (NS003154) and the National Institute on Aging (AG000935).
NINDS (https://www.ninds.nih.gov) the country’s leading study fund of the brain and nervous system. The mission of NINDS is to seek basic knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease.
About the National Institute on Aging (NIA): The NIA will lead the U.S. federal government’s effort to monitor and support aging and the health and well-being of the elderly. Visit the NIA website for information on a range of aging topics in English and Spanish. Learn more about age-related mental change and neurodegenerative diseases through the Alzheimer’s website and the Center for Related Dementias Education and Reference (ADEAR). Stay connected to NIA!
About the National Institutes of Health (NIH):
NIH, the nation’s medical research organization, comprises 27 Institutes and Centers and is part of the U.S. Department of Health and Human Services. NIH is the leading federal agency that conducts and supports basic, clinical, and translational medical examination, and examines the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
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