Researchers at Columbia University have identified a genetic variant that reduces the likelihood of developing Alzheimer’s disease by up to 70%, potentially protecting thousands of individuals in the United States from the disease. This discovery points to the role of the brain’s blood vessels in Alzheimer’s and could lead to new therapeutic approaches. The protective variant is found in a gene that produces fibronectin, a key component of the blood-brain barrier that controls the movement of substances in and out of the brain.
Excess levels of fibronectin in the blood-brain barrier have been linked to Alzheimer’s disease, and the identified variant appears to prevent this buildup, allowing for the clearance of toxic amyloid deposits from the brain. Studies in zebrafish and mice have confirmed this hypothesis, showing that reducing fibronectin levels can enhance amyloid clearance and improve other damage associated with Alzheimer’s. This suggests that targeting fibronectin could be a promising strategy for preventing or treating Alzheimer’s disease by mimicking the protective effect of the genetic variant.
Current treatments for Alzheimer’s disease focus on removing amyloid deposits, but they do not address the underlying damage or improve symptoms. The discovery of the protective fibronectin variant offers a new approach, potentially allowing for earlier and more effective clearance of amyloid through the bloodstream. These findings have implications for drug development, as targeting fibronectin could provide a strong defense against Alzheimer’s and repair damage caused by the disease.
The protective gene variant was identified in individuals who had inherited the APOEe4 gene, which significantly increases the risk of Alzheimer’s disease. By sequencing the genomes of APOEe4 carriers over the age of 70, the researchers uncovered the fibronectin variant in individuals who remained symptom-free despite carrying the APOEe4 gene. Collaborating with other research groups confirmed the presence of the variant and its protective effects, suggesting it could delay the onset of Alzheimer’s by approximately four years and reduce the risk of developing the disease by 71%.
The therapeutic potential of the fibronectin variant extends beyond APOEe4 carriers, as differences in fibronectin levels have been observed in individuals with Alzheimer’s disease regardless of their APOE status. Lowering fibronectin levels could offer protection against Alzheimer’s in a broader population, indicating that a drug targeting fibronectin could be a significant advancement in the fight against this debilitating condition. The widespread impact of this genetic variant highlights the importance of understanding the role of blood vessels in Alzheimer’s disease and developing targeted therapies to prevent and treat the condition.
