Stanford Medical Researchers and global collaborators have made a significant discovery regarding a common genetic factor that provides protection against both Alzheimer’s and Parkinson’s diseases. This genetic variant, known as DR4, is carried by approximately 20% of individuals and has been found to reduce the risk of these neurodegenerative conditions by over 10%. This breakthrough has potential implications for the development of future vaccines targeting these diseases.
The study involved a comprehensive analysis of medical and genetic data from diverse populations across several continents. It revealed that individuals with a specific variant of a gene associated with immune function, namely DR4, have a significantly lower risk of developing Alzheimer’s and Parkinson’s diseases.
In more accessible terms, approximately 1 in 5 people possess a unique gene variant that appears to offer resistance to both Alzheimer’s and Parkinson’s. This discovery suggests that individuals carrying the DR4 gene variant may be particularly receptive to potential vaccines aimed at slowing down or preventing these common neurodegenerative disorders.
The research also hints at a possible link between the tau protein and the development of both Alzheimer’s and Parkinson’s. Tau is notorious for accumulating in the brains of Alzheimer’s patients, and this study suggests it may have a mysterious role in Parkinson’s as well.
The study’s findings and implications are detailed in a recently published paper in the Proceedings of the National Academy of Sciences. Emmanuel Mignot, MD, Ph.D., Craig Reynolds Professor in Sleep Medicine, along with Michael Greicius, MD, and Jean-Charles Lambert, Ph.D., played key roles in this research.
The protective allele identified in the study is named DR4, and it appears to have a similar protective effect against both Parkinson’s and Alzheimer’s diseases. The researchers analyzed extensive medical and genetic databases from various regions globally, involving tens of thousands of patients with these conditions. They discovered that those carrying the DR4 gene variant had a roughly 10% reduction in their risk of developing these diseases.
The study also examined the brains of over 7,000 Alzheimer’s patients post-mortem, revealing that DR4 carriers had fewer neurofibrillary tangles, which are characteristic of Alzheimer’s. These tangles are strongly associated with the severity of the condition. Interestingly, DR4 also delayed the onset of symptoms in Parkinson’s patients, even though neurofibrillary tangles are not typically found in Parkinson’s.
The study suggests that tau, a central player in Alzheimer’s, may have an unknown role in Parkinson’s. However, the exact nature of this connection remains unclear.
DR4 is one of the alleles of the DRB1 gene, part of the human lymphocyte antigen complex (HLA), essential for the immune system. Different HLA alleles produce proteins that display fragments of internal proteins on the cell’s surface for immune recognition.
Mignot believes that DR4’s protective effect may be related to “protective autoimmunity.” It appears that DR4 recognizes a chemically modified segment of the tau protein, which might be causing issues.
The researchers focused on the acetylated PHF6 peptide, a modified segment of tau frequently found in Alzheimer’s brains. DR4 demonstrated a strong affinity for acetylated PHF6, which is known to facilitate tau aggregation into neurofibrillary tangles. This suggests that a vaccine containing acetylated PHF6 could potentially draw the immune system’s attention to this modified peptide, potentially interfering with tau’s aggregation. This approach may delay or slow the onset of Alzheimer’s and possibly Parkinson’s in individuals carrying protective DR4 variants.
However, it’s important to note that not all DR4 variants provide the same level of protection, and some may be more effective in certain populations. A blood test may be needed to determine who would benefit from such a vaccine.
In summary, this groundbreaking research has identified a genetic factor, DR4, that offers protection against both Alzheimer’s and Parkinson’s diseases. It also suggests a possible connection between tau protein and these neurodegenerative disorders, opening the door to potential therapies and vaccines in the future. The study involved collaboration from researchers worldwide and was supported by various funding sources, including the National Institutes of Health, the European Union, and several foundations and agencies. Furthermore, Stanford University’s office of technology licensing has filed a patent application based on the intellectual property associated with these findings.
