A genetic study conducted by NIH found that Lewy body patients were more likely to have Alzheimer’s or Parkinson’s than age-matched controls. Photo credit: Courtesy of the Scholz Lab NIH / NINDS.

In a study conducted by researchers from the National Institutes of Health (NIH), scientists found that five genes can play a critical role in determining whether a person has Lewy body dementia, a devastating disorder that the brain is littered with clumps of abnormal protein deposits on Lewy bodies. Lewy bodies are also a hallmark of Parkinson’s disease. The results, published in Nature Genetics, not only supported the disease’s links to Parkinson’s disease, but also suggested that people with Lewy body dementia might have genetic profiles similar to people with Alzheimer’s disease.

“Lewy body dementia is a devastating brain disorder for which we have no effective treatments. Patients appear to suffer from the worst of Alzheimer’s and Parkinson’s diseases. Our results support the idea that this may be because Lewy bodies -Dementia is caused by a spectrum of problems that can occur with either condition, “said Dr. med. Sonja Scholz, researcher at the National Institute for Neurological Diseases and Stroke (NINDS) of the NIH and lead author of the study. “We hope these results will serve as a blueprint for understanding the disease and developing new therapies.”

The study was conducted by Dr. Scholz’s team and researchers in the laboratory led by Bryan J. Traynor, MD, Ph.D., Senior Investigator at the National Institute on Aging (NIA) at the NIH.

Lewy body dementia usually affects people over the age of 65. Early signs of the disease include hallucinations, mood changes, and problems with thinking, moving, and sleeping. Patients who have initial cognitive and behavioral problems are usually diagnosed with dementia with Lewy bodies, but sometimes they are mistakenly diagnosed with Alzheimer’s. Alternatively, many patients initially diagnosed with Parkinson’s disease may experience difficulty thinking and mood caused by Lewy body dementia. In both cases, as the disease progresses, patients become severely disabled and may die within 8 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 gene for alpha-synuclein (SNCA), the main protein in Lewy bodies. Further studies have shown that variants of the gene for apolipoprotein E (APOE), which is known to play a role in Alzheimer’s disease, may also play a role in Lewy body dementia.

The genetic study of Lewy body dementia supports the link to Alzheimer's and Parkinson's

A study conducted by NIH found that the sequences of five genes can help determine if a person has Lewy body dementia, a devastating brain disorder. Photo credit: Courtesy of Scholz Lab, NIH / NINDS.

“Very little is known about the genetic powers behind Lewy body dementia compared to other neurodegenerative diseases,” 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 Lewy body dementia patients with those of 4,931 healthy, age-appropriate control persons. Samples were collected from participants of European descent at 44 locations: 17 in Europe and 27 in North America. DNA sequencing was led by Clifton Dalgard, Ph.D. and researchers at the American Genome Center, a series of state-of-the-art laboratories at the Uniformed Services University of 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 found in Lewy body dementia patients were often different from those in controls, suggesting that these genes may be important. It was the first time that two of the genes, BIN1 and TMEM175, were involved in the disease. These genes can also be linked to Alzheimer’s and Parkinson’s. The other three genes, SNCA, APOE and GBA, had been involved in previous studies and thus strengthened the role of the genes in Lewy body dementia.

The researchers also saw differences in the same five genes when they compared the DNA sequences of an additional 970 Lewy body dementia patients to a new set of 8,928 control subjects, confirming their initial results.

Further analysis indicated that changes in the activity of these genes can lead to dementia and that the GBA gene can 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 sugary fats. The researchers found that both common and rare variants of the GBA gene are related to Lewy body dementia.

“These results provide a list of five genes that we strongly suspect may play a role in Lewy body dementia,” said Dr. Traynor.

Eventually, to examine the obvious links between Lewy body dementia and other neurodegenerative diseases, the researchers analyzed data from previous studies on Alzheimer’s and Parkinson’s diseases. They found that the genetic profiles of the patients in this study were more likely to have Alzheimer’s or Parkinson’s than the age-matched controls. These predictions held true after decreasing the potential effects of known Alzheimer’s and Parkinson’s genes like APOE and SNCA. Interestingly, the patient’s genetic risk profiles for Alzheimer’s disease on the one hand and Parkinson’s disease on the other did not overlap.

“Although Alzheimer’s and Parkinson’s are molecularly and clinically very different diseases, our results support the idea that the problems that cause these diseases can also occur in Lewy body dementia,” said Dr. Scholz. “The challenge in treating these patients is determining what specific problems are causing dementia. We hope that studies like these doctors will help find precise treatments for each patient’s condition.”

To support these efforts, the team published the genome sequence data from the study on the Genotypes and Phenotypes Database (dbGaP), a website of the National Library of Medicine, on which researchers are free to seek new knowledge about the causes of Lewy body dementia and others can seek interference.

Signs and symptoms of Lewy dementia

More information:
Chia, R. et al. Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insight into the complex genetic architecture. Nature Genetics, February 15, 2021 DOI: 10.1038 / s41588-021-00785-3 Provided by National Institutes of Health

Quote: Lewy Body Dementia Genetic Testing Supports Links to Alzheimer’s and Parkinson’s (2021, February 16), accessed February 16, 2021 from https://medicalxpress.com/news/2021-02-genetic-lewy-body- dementia-ties.html

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