The gene that protects against Alzheimer's: «It creates a barrier in the brain»

The main risk factor for dementia, and in particular Alzheimer's disease, is age. However, on the genetic planthe presence of a gene responsible for the production of a protein called apolipoprotein E, (ApoE), in particular theApoE4, makes the disease more likely. But not all patients with ApoE4 develop Alzheimer's, why?

The protein fibronectin

A group of researchers from Columbia University (New York) wanted to investigate the reason, looking to see if there were genes that modulated the effect of this risk factor. In their work published in the journal Acta Neuropathologicawhere they analyzed data from 11 thousand people, the researchers discovered that the expression of a protein, the fibronectinproduced by a gene, had particularly low levels in individuals who carried ApoE4 but did not develop Alzheimer's. “The suspicion is that the gene that encodes this protein could be a determining factor in influencing the risk effect of Alzheimer's disease and cognitive decline linked to ApoE4” he explains Alessandro Padovanipresident of the Italian Society of Neurology.

Zebrafish analysis

To validate the observational study on humans, scientists genetically modified the zebra fishorganisms used to study human pathologies of genetic origin, confirming that fish with high levels of fibronectin developed glial and vascular alterations very similar to those observed in moles patients with Alzheimer's. They also found that reducing fibronectin in animals increased amyloid removalimproving the disease.

Where is fibronectin found?

Fibronectin is usually present in the blood-brain barrier in very limited quantities, but the level increases greatly in people with Alzheimer's. According to the authors of the research, fibronectin, if knocked out by a genetic mutation, can protect those who carry ApoE4 from the neurodegenerative disease. Since fibronectin is a component of the blood-brain barrier, a sort of filter that surrounds the blood vessels of the brain and regulates the passage of substances, scientists have hypothesized that by modifying this filter by blocking fibronectin it is possible to prevent its accumulation in the brain.

Future

Where can this research take us? «We may be able to develop new types of therapies that mimic the protective effect of the gene to prevent or treat the disease,” he explains Caghan Kizil, among the authors of the study. «If we were able to block the production of this protein we could reduce or mitigate the risk of Alzheimer's disease not only in ApoE4 carriers, but also in those with other risk factors» adds Alessandro Padovani, who is also director of the Neurological Clinic at Spedali Civili of Brescia and professor of Neurology at the University of the city.

Lifestyles

However, research is still very long and it will take years to understand if it will really be possible to create a therapy that imitates the protective variant. Today we can do much more by following correct lifestyles: hypertension, smoking, obesity, diabetes, sedentary lifestyle, alcohol consumption, poor education are among the major risk factors for Alzheimer's disease.