Key Takeaways:
- Study is the first to find that rare genetic variants linked to other neurodegenerative disorders – especially Parkinson’s disease – increase the risk of developing amyotrophic lateral sclerosis (ALS)
- Having these rare variants may lead to faster ALS progression and shorter survival
- Although having these variants won’t change the treatment, people who have them should be closely monitored for symptoms and progression by their doctors
News — ORLANDO, Fla., Sept. 16, 2024 – People with rare genetic variants associated with Parkinson’s disease and other neurodegenerative disorders are at increased risk of developing amyotrophic lateral sclerosis (ALS), according to new research presented at the 149th Annual Meeting of the (ANA).
The study is the first to find that rare variants linked to other neurodegenerative diseases are associated with ALS, also known as Lou Gehrig’s disease. Researchers also found having these rare variants raises the risk of faster progression of ALS as well as shorter survival.
“Our findings broaden the understanding of the genetic overlap between ALS and these other disorders by focusing on rare variants instead of common genetic factors,” said Maurizio Grassano, M.D., lead author of the study and a postdoctoral researcher and neurologist at the ALS Center, University of Turin, Italy. “Although identifying these variants may not change treatment, the knowledge can help physicians personalize management of those patients.”
Possessing these genetic variants does not necessarily cause ALS, but this information could aid clinicians in monitoring individuals who may be at increased risk for the disease, he said. The information also can help families understand potential risks and make informed decisions. About 10% of people with ALS have a family history of the disease. In this study, the researchers excluded people with ALS whose disease could be directly attributed to known ALS genetic mutations.
The researchers gave genetic panel tests for 153 neurodegeneration-associated genes to 791 people with ALS and 757 healthy people without the disease. Among the ALS patients, 145 (18.3%) carried at least one high-impact variant in neurodegenerative genes and 90 (11.4%) had a mutation that hadn’t previously been discovered (novel). Comparatively, in the control group, 107 (14.4%) carried a genetic variant, and 51 (6.9%) had a novel mutation. The researchers determined that carriers of a variant in a neurodegeneration-related gene have a 1.3 times higher risk of developing ALS and a 1.8 times greater risk if the variant was novel or ultra-rare. The higher percentage of these variants among ALS patients suggests that individuals with ALS have a greater likelihood of carrying genetic mutations associated with other neurodegenerative diseases, which may have increased their risk of developing ALS.
The strongest link was Parkinson’s disease. Those who had genes associated with Parkinson’s disease had a 3.6 times greater risk of developing ALS than those who did not have those genetic variants. Beyond Parkinson’s disease, the researchers determined the strongest risk for ALS was associated with genetic variants for peripheral neuropathies. They did not find an increased risk of ALS among those with genetic variants linked to other neurodegenerative diseases such as muscular dystrophies or spastic paresis.
The authors said their research suggests that ALS and other neurodegenerative diseases may share a common mechanism. For example, they note the lysosomal pathway—a cellular process that involves the breakdown and recycling of materials within a cell—may play a larger role in the disease than previously thought. The lysosomal pathway is known to be interrupted in Parkinson’s disease, and this research suggests it may play a critical role in the degeneration of motor neurons in ALS.
“In this era of extensive genetic testing, it has become increasingly likely that variants in genes will be detected that are not directly linked to the primary diagnosis,” said Dr. Grassano. “These insights will help inform future research on diagnosing and treating this devastating disease.”
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About the American Neurological Association (ANA)
From advances in stroke and dementia to movement disorders and epilepsy, the has been the vanguard of research since 1875 as the premier professional society of academic neurologists and neuroscientists devoted to understanding and treating diseases of the nervous system. Its monthly Annals of Neurology is among the world’s most prestigious medical journals, and the ANA’s Annals of Clinical and Translational Neurology is an online-only, open access journal providing rapid dissemination of high-quality, peer-reviewed research related to all areas of neurology. The acclaimed ANA Annual Meeting draws faculty and trainees from the top academic departments across the U.S. and abroad for groundbreaking research, networking, and career development. For more information, visit or .
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