News Release
Tuesday 16 February 2021
NIH-led study found five genes that could play a critical role in Lewy body dementia.
In a study led by National Institutes of Health researchers, scientists found that five genes could play a critical role in determining whether someone would suffer from Lewy dementia, a devastating disorder that flushes the brain with clumps of abnormal protein deposits. which are called Lewy bodies. Lewy bodies are also a feature of Parkinson’s disease. The results, published in Nature Genetics, not only support the links of the disease with Parkinson’s disease, but also suggest that people with Lewy dementia may share similar genetic profiles as those with Alzheimer’s disease.
‘Lewy body dementia is a devastating brain disorder for which we have no effective treatments. Patients often appear to suffer the most from Alzheimer’s and Parkinson’s disease. Our results support the idea that it may be because Lewy’s body dementia is caused by a spectrum of problems that can be seen in both disorders, ‘said Sonja Scholz, MD, Ph.D., researcher at the NIH’s National Institute of Neurological Disorders and Strokes (NINDS) and the senior author of the study. “We hope these results serve as a blueprint 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’s National Institute on Aging (NIA).
Lewy dementia in the body usually occurs in people older than 65 years. Early signs of the disease include hallucinations, moodiness and difficulty thinking, moving and sleeping. Patients who initially have cognitive and behavioral problems are usually diagnosed with 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 problems with thinking and mood caused by Lewy dementia. In both cases, if the disease worsens, patients become severely disabled and may die within eight years of diagnosis.
An increasing body of evidence suggests that genetics may play a role in the disease and that some cases may be inherited. Scientists have found that some of these rare cases can be caused by mutations in the gene for alpha-synuclein (SNCA), the major protein found in Lewy bodies. Further studies have found that variants in the gene for apolipoprotein E (APOE), which is known to play a role in Alzheimer’s disease, may also play one in Lewy dementia.
“Compared to other neurodegenerative disorders, very little is known about the genetic forces behind Lewy dementia,” said Dr. Traynor said. “To gain 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 Lewy dementia with those of 4,931 healthy, age-adjusted control participants. Samples were collected from participants of European descent at 44 locations: 17 in Europe and 27 in North America. The DNA sequence was led by Clifton Dalgard, Ph.D., and researchers from The American Genome Center, a series of modern laboratories at the Uniformed Services University of the Health Sciences and supported by the Henry M. Jackson Foundation for the Advancement of military medicine.
Initially, they found that the sequences of five genes of the patients with Lewy dementia often differed from those of the controls, suggesting that these genes may be important. It was the first time that two of the genes, called BIN1 and TMEM175, were involved 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, thus reinforcing the importance of the 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 Lewy dementia with a new set of 8,928 controls, confirming their initial results.
Further analysis suggested that changes in the activity of these genes could lead to dementia and that the GBA gene could have a particularly strong influence on the disease. The gene encodes instructions for beta-glucosilceramidase, a protein that helps the cell’s recycling system break down sugar fats. The researchers found that common and rare variants in the GBA gene were linked to Lewy dementia.
“These results list five genes that we strongly suspect play a role in Lewy dementia,” said Dr. Traynor said.
Finally, to investigate 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 Alzheimer’s or Parkinson’s disease than at age temperature. These predictions occurred even after they diminished the potential impact of known Alzheimer’s and Parkinson’s disease – causing genes, 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 hand do not overlap.
“Although Alzheimer’s and Parkinson’s disease are molecularly and clinically very different disorders, our results support the idea that the problems that cause the diseases can also occur in Lewy dementia,” Dr. Scholz said. ‘The challenge we face in treating these patients is to determine what specific problems the dementia is causing. We hope that studies like these doctors will help to find exact treatments for each patient’s condition. ”
To aid this effort, the team published the genome sequence of the study on the Genotype and Phenotypes Database (dbGaP), a website of the National Library of Medicine, where researchers can freely search for new insights into the causes of Lewy- body dementia and other disorders.
Article:
Chia, R., et al. Genome sequence analysis identifies new loci associated with Lewy body dementia and provides insight into the complex genetic architecture. Natural Genetics, 15 February 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 for Aging (AG000935).
NINDS (https://www.ninds.nih.gov) is the country’s leading funder for research into the brain and nervous system. The mission of NINDS is to acquire fundamental knowledge about the brain and nervous system and use that knowledge to reduce the burden of neurological diseases.
About the National Institute for Aging (NIA): NIA is leading the U.S. federal government’s efforts to conduct and support research on aging and the health and well-being of older people. Visit the NIA website for information on a range of older topics in English and Spanish. Learn more about age-related cognitive change and neurodegenerative diseases via the Alzheimer’s and related dementia education and referral website (ADEAR). Stay connected with NIA!
About the National Institutes of Health (NIH):
NIH, the country’s medical research agency, contains 27 institutes and centers and is part of the U.S. Department of Health and Human Services. NIH is the primary federal agency that conducts and supports basic, clinical, and translational medical research, investigating the causes, treatments, and drugs for common and rare diseases. Visit www.nih.gov for more information on NIH and its programs.
NIH… To turn discovery into health®