Protective Allele Provides Resistance To Alzheimer's And Parkinson's Diseases

Monday - December 11 2023, 18:32 UTC - 11 months ago

A large-scale analysis of medical and genetic data by Stanford Medicine researchers and their collaborators has revealed that a specific gene variant (DR4) might provide resistance to Alzheimer's and Parkinson's diseases in around 20% of the population. The study was published in the Proceedings of the National Academy of Sciences.

A large-scale analysis of medical and genetic information revealed that individuals carrying a specific variant of a gene linked to immune function had a reduced risk of developing Alzheimer’s and Parkinson’s diseases. Approximately 1 in 5 individuals possess a specific gene variant that seems to offer resistance to both Alzheimer’s and Parkinson’s diseases. This discovery, made by Stanford Medicine researchers and their collaborators, suggests that these individuals might particularly benefit from a future vaccine aimed at slowing or halting these common neurodegenerative disorders.

An analysis of medical and genetic data from hundreds of thousands of people of diverse ancestries from several continents has revealed that carrying this gene version, or allele, reduced people’s chances of contracting either Parkinson’s or Alzheimer’s by more than 10% on average.

The evidence suggests that a protein called tau, which is notorious for aggregating in the brains of Alzheimer’s patients, may also be involved, in some mysterious way, in the development of Parkinson’s disease.

The findings and implications are described in a paper recently published in the Proceedings of the National Academy of Sciences. Emmanuel Mignot, MD, Ph.D., the Craig Reynolds Professor in Sleep Medicine and a professor of psychiatry and behavioral sciences, shares senior authorship with Michael Greicius, MD, the Iqbal Farrukh and Asad Jamal Professor and a professor of neurology and neurological sciences, and Jean-Charles Lambert, Ph.D., director of research for Inserm at the University of Lille in France. Lead authors are Yann Le Guen, Ph.D., assistant director of computational biology in Stanford Medicine’s quantitative sciences unit; Guo Luo, Ph.D., an instructor of sleep medicine; former postdoctoral scholar Aditya Ambati, Ph.D.; and Vincent Damotte, Ph.D., a bioinformatician associated with Lambert’s group.

The protective allele identified in the study is called DR4.

“In an earlier study we’d found that carrying the DR4 allele seemed to protect against Parkinson’s disease,” Mignot said. “Now, we’ve found a similar impact of DR4 on Alzheimer’s disease.” .

The Stanford Medicine team combined dozens of medical and genetic databases collected from numerous countries — in Europe, East Asia, the Middle East, and South and North America. All told, the databases included more than 100,000 people with Alzheimer’s disease and more than 40,000 with Parkinson’s disease. The scientists contrasted the incidence and age of onset of Alzheimer’s and Parkinson’s among people with DR4 versus those without it and found a roughly 10% risk reduction in those carrying DR4.

“That this protective factor for Parkinson’s wound up having the same protective effect with respect to Alzheimer’s floored me,” Mignot said. “The night after we found that out, I couldn’t sleep.” .

The investigators also analyzed data from the autopsied brains of more than 7,000 Alzheimer’s patients from the Religious Orders Study and the Memory and Aging study, both based at Rush University in Chicago. The scientists looked for evidence of the DR4 variant among the cells lining the blood vessels that feed into and out of the brain.

“This gene variant appeared to somehow affect these cells so they were more likely to prevent the entry into the brain of deleterious material that then contributes to the development of Parkinson’s and Alzheimer’s,” Mignot said.

While the researchers pursued the mechanisms underlying DR4’s protective properties, Mignot noted several implications.

“At the very least, this finding suggests that we should consider the DR4 variant as part of risk-assessment and monitoring for clinical trial data for both Alzheimer’s and Parkinson’s,” he said. “Looking further down the road, we hope that vaccines or medications aimed at preventing these disorders could take the protective effects of DR4 into account.” .

The team will continue to explore ongoing and planned clinical trials to see if they can validate the findings’ relevance to Alzheimer’s and Parkinson’s diseases.