In a study led by National Institutes of Health (NIH) researchers, 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 riddles the brain with clumps of abnormal protein deposits called Lewy bodies, according to a news release from NIH.
Lewy bodies are also a hallmark of Parkinson’s disease. The results, published in Nature Genetics, not only supported the disease’s ties to Parkinson’s disease but also suggested that people who have Lewy body dementia may share similar genetic profiles to those who have Alzheimer’s disease.
Lewy body dementia usually affects people over 65 years old. Early signs of the disease include hallucinations, mood swings, and problems with thinking, movements, and sleep. Patients who initially have cognitive and behavioral problems are usually diagnosed as having dementia with Lewy bodies, but are sometimes mistakenly diagnosed with Alzheimer’s disease. Alternatively, many patients who are initially diagnosed with Parkinson’s disease may eventually have difficulties with thinking and mood 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 genetics may play a role in the disorder 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 main 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 body dementia.
Researchers compared the chromosomal DNA sequences of 2,981 Lewy body dementia patients with those of 4,931 healthy, age-matched control participants. Samples were collected from participants of European ancestry at 44 sites: 17 in Europe and 27 across North America.
Initially, researchers found that the sequences of five genes from the Lewy body dementia patients were often different 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, had been implicated in the disease. These genes may also have ties to Alzheimer’s and Parkinson’s diseases. The other three genes, SNCA, APOE, and GBA, had been implicated in previous studies, and thus, strengthened 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 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 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 sugary fats. The researchers found that both common and rare variants in the GBA gene are tied to Lewy body dementia.
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 had higher chances of suffering from either Alzheimer’s or Parkinson’s disease than the age-matched control subjects. These predictions held even after they lowered the potential impact of known Alzheimer’s and Parkinson’s disease-causing genes, like APOE and SNCA.
