Researchers pinpoint gene mutation potentially reducing chances for Alzheimer's disease associated with APOE ε4 factor
In a significant breakthrough, a new study published in Acta Neuropathologica has uncovered a rare variation of the fibronectin 1 (FN1) gene that reduces the odds of developing Alzheimer's disease by an impressive 71%. This discovery challenges the previous understanding of how Alzheimer's risk works, suggesting that even among the genetically "doomed," some are spared by a hidden genetic defense system.
The study focuses on the protective mechanisms of the FN1 gene, which could potentially be replicated in people who didn't inherit the rare variant naturally. The researchers, supported by grants from the National Institute on Aging (NIA), focused on adults over 70 who had two copies of the APOE ε4 gene but showed no signs of cognitive decline. Interestingly, a disproportionate number of these cognitively healthy seniors carried rare variants of FN1.
The FN1 gene codes for fibronectin, a protein involved in how cells stick to each other and to their surroundings. In the brain, fibronectin plays a key role in the blood-brain barrier, acting as a gatekeeper for what enters the brain. Those who developed Alzheimer's disease, according to the study, had more fibronectin 1 protein in the blood-brain barrier compared to those who didn't, despite carrying the APOE ε4 gene.
The excess fibronectin 1 protein might disrupt the barrier, potentially allowing harmful substances to leak into the brain and trigger or accelerate neurodegeneration. However, individuals with protective versions of FN1 tend to have less fibronectin protein accumulating in their brain's blood vessels.
The study highlights the potential for a new type of Alzheimer's treatment that modulates the behaviour of the blood-brain barrier, rather than just targeting amyloid plaques or tau tangles. The long-term goal is to develop new therapies that can mimic nature's secret protection, potentially offering hope for the millions of people genetically at risk for Alzheimer's disease.
Carrying two copies of the APOE ε4 gene significantly increases the odds of developing Alzheimer's disease. Yet, not everyone with two copies of the APOE ε4 gene develops the disease. The scientists went further and found that those with the rare FN1 variant were dramatically less likely to develop Alzheimer's disease, even with two copies of the APOE ε4 gene.
The study underscores the message that risk is not fate, and even people with high-risk genes can thrive. Further research is needed to fully understand the mechanisms by which this FN1 variation exerts its protective effect against Alzheimer's disease. Scientists are already exploring why less fibronectin at the blood-brain barrier is beneficial, the feasibility of FN1 gene therapy, how FN1 interacts with other protective or risk-related genes, and the role of fibronectin in other neurological conditions beyond Alzheimer's.
The new study in Acta Neuropathologica reveals a rare FN1 gene variation that significantly reduces the risk of Alzheimer's disease, even among those with high-risk genes like APOE ε4. This research opens possibilities for a novel treatment approach in health-and-wellness, targeting the behavior of the blood-brain barrier to combat Alzheimer's disease, alongside exploring the FN1 gene's role in other neurological disorders, such as medical-conditions like Alzheimer's disease and other neurological disorders.
