Stanford Medicine and international collaborators have discovered that around 20% of individuals carry genetic mutations that reduce their risk of Alzheimer’s disease or Parkinson’s disease by 10% or more. This particular variant, known as DR4, has the potential to enhance future vaccines for these neurodegenerative diseases. In addition, the study found a potential link between the tau protein and both diseases, providing new possibilities for targeted therapies and vaccines.
The large-scale analysis included medical and genetic information from a wide range of individuals across different continents. This data analysis revealed that certain gene variants related to immune function are associated with a lower risk of developing Alzheimer’s and Parkinson’s diseases. Approximately one in five people possess a specific genetic mutation that provides resistance to both diseases.
The research, led by Stanford Medicine, indicates that individuals with this protective genetic mutation may be less likely to benefit from future vaccines aimed at slowing or stopping the progression of these common neurodegenerative diseases. Results from the analysis of medical and genetic data from hundreds of thousands of people from diverse backgrounds confirmed that carrying the DR4 allele increased the average chance of developing Parkinson’s or Alzheimer’s disease by more than 10%. New evidence has also surfaced suggesting that the tau protein, which is known for aggregating in the brains of Alzheimer’s patients, may also play a role in the development of Parkinson’s disease.
The study, published in the Proceedings of the National Academy of Sciences, was a collaboration between researchers at Stanford Medicine and international partners. The researchers involved in this study were Emmanuel Mignot, MD, Michael Gracius, MD, Iqbal Farooq, and Asad Jamal from Stanford Medicine, as well as Dr. Jean-Charles Lambert from Inserm, University of Lille, France. The lead author was Yan Le Nguyen, Ph.D., and other contributors included Dr. Guo Luo, Dr. Aditya Ambati, and Dr. Vincent Damot.
Further findings from the study showed that individuals with the DR4 allele were more likely to develop neurofibrillary tangles, characteristic of Alzheimer’s disease, in their brains. The study also suggests that tau, a protein central to Alzheimer’s disease, may have an unknown role in Parkinson’s disease.
DR4 is a particular allele of the DRB1 gene, which is a part of the human lymphocyte antigen complex. This complex is crucial in allowing the immune system to recognize the internal contents of cells. One of the significant findings of this study was that the specific peptide fragment that DR4 recognizes and presents is a chemically modified segment of the tau protein, which plays a role in both diseases. The study suggests that the DR4 allele could be used to create a vaccine targeting this modified peptide as a potential way to interfere with tau aggregation and the development of these neurodegenerative diseases. There may be potential to delay or slow the progression of the diseases in individuals who carry the protective variants of DR4.
The study also noted that the effectiveness of the vaccine may depend on the subtype of DR4 a person carries, which varies among different ethnic groups. For example, one subtype of DR4 that is more common among East Asians may be less protective against neurodegenerative diseases.
Source: scitechdaily.com
