Emmanuel Mignot discusses the potential protective effects of a variant of an immune system gene against neurodegenerative diseases. The podcast explores the role of HLA genes in the immune system, their association with Parkinson's and Alzheimer's diseases, and the potential mechanism for efficient removal of tau protein. The researchers also propose a potential immune system mechanism in clearing acetylated tau to prevent neurodegenerative diseases. Additionally, the podcast explores the potential of a vaccine to protect against neurodegenerative diseases by enhancing the immune response and clearing tau aggregates.
A specific genetic variant of the HLA system, HLA D4, may offer protection against neurodegenerative diseases like Alzheimer's and Parkinson's, opening the door for potential vaccine development.
The HLA system's allele DR4, when triggered, can recognize and clear tau protein aggregates, suggesting a potential immune-based approach to slowing disease progression.
Deep dives
Role of Tau in Neurodegenerative Diseases
Tau protein is implicated in various neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and Lou Gehrig's disease. Neurofibrillary tangles, composed mostly of aggregated tau, are a hallmark of these conditions. Researchers discovered that a specific genetic variant of the Human Leukocyte Antigen (HLA) system, known as HLA D4, may provide protection against these diseases. This finding opens up the possibility of developing a vaccine that can further enhance the protective effect of HLA D4 and slow disease progression.
HLA and Immune Response to Tau
The study revealed that certain alleles of the HLA system, particularly DR4, are associated with reduced tau aggregation and neurofibrillary tangles. DR4 appears to bind to an acetylated form of a specific region of the tau protein, PHF6, which plays a crucial role in tau aggregation. This suggests that the immune system, when triggered by DR4, can recognize and clear tau as if it were a pathogen. The researchers speculate that strengthening this immune response, possibly through a vaccine, could enhance the clearance of tau aggregates and mitigate disease progression.