Even after several efforts, researchers are yet to find what exactly causes dementia, which affects 32 million people globally. However, they do know that genetics plays a role, specifically some genetic variants, which include a mutation or change in a gene’s DNA that causes it to act differently.
Searching and studying genetic variants in Alzheimer’s disease is a significant study area. For example, scientists have discovered that genetic variants of the APOE gene and myeloid cell 2 (TREM2) may be tied to Alzheimer’s disease.
According to a study published in the journal Acta Neuropathologica, researchers believe that people with a mutation in the fibronectin gene are protected against Alzheimer’s disease since it helps stop the buildup of too much fibronectin in the blood-brain barrier. Fibronectin is an adhesive glycoprotein found on cell surfaces and in the blood and helps with certain cell functions. This substance is found in the blood-brain barrier, which helps control things that move in and out of the brain. Previous research shows that people with Alzheimer’s disease have higher fibronectin concentration in their blood than those without.
Researchers also discovered that the protective fibronectin gene variant occurred in people who never developed symptoms of Alzheimer’s disease. However, they had inherited the e4 form of the APOE gene, which previous research shows significantly increases a person’s risk of developing the disease.
Genetic data of several hundred people over 70 also carried the APOEe4 genetic variant. Study participants were from various ethnic backgrounds, and some did have Alzheimer’s disease.
After combining their study results with those from replicated studies conducted at Stanford and Washington Universities, researchers found the fibronectin gene variant lowered Alzheimer’s disease risk by 71% in people carrying the APOEe4 gene variant.
It was concluded that Alzheimer’s disease may start with amyloid deposits in the brain, but the disease manifestations are the result of changes that happen after the deposits appear. Findings suggest that some of these changes occur in the brain’s vasculature and that we may be able to develop new types of therapies that mimic the gene’s protective effect to prevent or treat the disease.
This study suggests a possible mechanism for disrupting the blood-brain barrier and a pathway to prevent or correct this disruption. It is exciting that researchers are looking at multiple pathways for the etiology of Alzheimer’s. It will be helpful to get confirmation of these findings and applications in finding a potential cure or prevention of this debilitating disease.
Journal Reference – Bhattarai, P., Gunasekaran, T. I., Belloy, M. E., Reyes-Dumeyer, D., Jülich, D., Tayran, H., … Vardarajan, B. N. (2024). Acta Neuropathologica, 147(1). doi:10.1007/s00401-024-02721-1
