A new study reveals five genes associated with Lewy body dementias. It supports that state and both associations. Parkinson’s disease And Alzheimer’s disease..
The study, led by researchers at the National Institutes of Health, Published online February 15 Nature genetics..
“Lewy body dementias is a catastrophic brain disorder for which there is no effective cure. Patients often appear to suffer from the worst of both Alzheimer’s and Parkinson’s diseases,” he said. Senior author Sonya Schorz, MD, said.
“Our results support the idea that this may be due to the various problems seen in both disorders of Lewy body dementias,” she said. “We hope that these results will serve as a blueprint for understanding the disease and developing new treatments.”
In this study, the researchers compared the chromosomal DNA sequences of 2981 patients with Lewy body dementias to the chromosomal DNA sequences of 4391 healthy, age-matched control participants. Samples were collected from participants of European ancestry at 44 sites (17 in Europe and 27 across North America).
The sequence of the five genes can help determine if a person suffers from Lewy body dementias. Credits: Scholz lab, NIH / NINDS
“We have a gene mutation GBA, BIN1, TMEM175, SNCA-AS1,and APOE It affects the risk of developing Lewy body dementias. ” Scholze, head of the Neurodegenerative Diseases Research Unit at the National Institute of Neurological Disorders, said stroke (NINDS), said Medscape Medical News..
Two of the genes were the first — BIN1 And TMEM175 — I was involved in this illness. The other three genes, SNCA, APOE, And GBAHas strengthened the importance of the gene in Lewy body dementias because it was associated with previous studies, researchers report.
They also validated the results in a second analysis in which a new set of another 970 patients with Lewy body dementias and 8928 control subjects showed differences in the same five genes.
Research into the exact functioning of these common risk variants is still underway, Scholz said. “What we know at this point is that they are involved in basic cellular processes such as protein transport, proteolysis, energy and lipid metabolism,” she said. “The end result is the loss of neuroprotective function and the acquisition of toxic function, resulting in protein accumulation, impaired mitochondrial respiratory capacity, inflammation, and neurotoxicity.”
These latest genetic discoveries confirm a strong association between Lewy body dementias, Parkinson’s disease, and Alzheimer’s disease.
“Interestingly, all five risk loci found to be associated with Lewy body dementias have been shown to play a role in either Alzheimer’s disease or Parkinson’s disease,” Scholz said. Stated.
“It seems that the genetic structure of Lewy body dementias has been shown to be very complex. Patients with Lewy body dementias have all the genetic features of Alzheimer’s disease and all the genetics of Parkinson’s disease. It does not have any characteristics. Here, the loci of Alzheimer’s disease, the loci of Parkinson’s disease, etc. overlap only in specific ways. This is the attraction of this disease, and our research describes this nuance. It represents the first step in elucidating. “
Although Alzheimer’s disease 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 dementias. The challenge faced in treating these patients is to identify specific problems. We hope that such studies will help doctors find the right treatment for each patient’s condition. I am. “
Researchers say they hope that shared mutants and nodes in common disease pathways will be targets for the development of disease-modifying therapies. “Knowing which molecular relationships exist between degenerative diseases will inform the design of clinical trials and facilitate the diversion of drugs to a wide range of diseases,” Scholz suggested.
She concluded that: “Our main take-away message from this study is that Lewy body dementias is a genetically complex, multigenic disorder that molecularly intersects with Alzheimer’s and Parkinson’s disease. We have released the raw data for access by researchers. We analyze the data with our own theories in mind, which we hope will accelerate the pace of discovery in this under-researched area. hoping.”
comment Medscape Medical NewsDr. James Beck, Chief Scientific Officer of the Parkinson’s Foundation, said this is one of the largest reports on the genetics of Lewy body dementias.
“This is a very interesting treatise that put a lot of effort into putting together all this genetic information from patients with Lewy body dementias,” said Beck, who was not involved in the study.
He pointed out observations that some genes are also associated with the relationship between Alzheimer’s disease or Parkinson’s disease and the clinical manifestations found in various conditions.
“Lewy body dementias is considered to be somewhere in the hell between Alzheimer’s disease and Parkinson’s disease. It is now a more specific subtype of neurodegenerative disease, as reported here. We recognize that good genetic discoveries can help with this. “
He said that one of the genes highlighted in this report is SNCAIs an antisense gene for α-synuclein, a protein at the heart of Lewy body dementias and Parkinson’s disease.
“This antisense gene is probably a regulator of α-synuclein production, which could be a target for drugs to down-regulate the process,” Beck suggested.
“It’s not a silver bullet, but this study is part of the process of developing information resources that bring precision medicine to neurodegenerative diseases,” Beck commented. “It gives us instructions for identifying specific genetic targets. We have to think about the functionality of different genes and mutations — what they do and they can be regulated. Is it? “
“In the future, we will be able to use genetic information in middle age to assess an individual’s risk of developing various neurodegenerative conditions and develop specific therapies that can delay this process. It’s just the beginning of that journey in that we are beginning to understand how genetics affects neurodegenerative diseases. ”
This study was partially supported by the National Institute of Health, the National Institute on Aging, and the National Institute for Neurological Disorders and Stroke on-campus research programs.
Nature genetics.. Published online on February 15, 2021. Overview
