Blood-brain barrier disrupted in hereditary frontotemporal dementia News
In patients with a hereditary form of frontotemporal dementia the blood-brain barrier is disrupted. This has been shown by research conducted by the University Medical Centre Groningen and Erasmus MC.

The blood-brain barrier of patients with a certain hereditary form of frontotemporal dementia (FTD) does not function properly. This was discovered by researchers at the UMCG and Erasmus MC who published their study in the scientific journal Nature Neuroscience [https://rdcu.be/cSmBg].   

Patients with frontotemporal dementia develop symptoms of dementia at a relatively early age. This hereditary form of FTD is caused by a mutation in the progranulin gene in thirty percent of  the cases. Nothing was known yet about what malfunctions in the brain of people with this hereditary form of FTD. Previous research suggested that the immune cells of the brain play a role, but thisnew research points in a different direction.   

The researchers from Rotterdam and Groningen compared brain tissue from thirteen FTD patients with the progranulin mutation with brain tissue from seven deceased people without a brain disease. The researchers studied cells other than neuronal cells in great detail. 'To do this, we used a technique called single-nucleus RNA sequencing, a way of determining which genes are active in individual cells. The question was: has this changed in FTD?' explains neuroscientist Prof. Dr. Bart Eggen of the UMCG. He led the study together with neurologist Prof. Dr. John van Swieten of Erasmus MC.   

The researchers found signs of disease particularly in the blood vessel cells of FTD patients. Compared to the healthy brain, many genes associated with a disruption of the blood-brain barrier were active. This is a network of blood vessels that allows nutrients to pass through and blocks harmful substances. The immune cells know as ‘microglia’ of the FTD brain looked relatively healthy.   

The findings are in line with what was already known about the progranulin gene. It is involved in blood vessel formation elsewhere in the body. So it is not surprising that a progranulin mutation also leads to blood vessel problems in the brain.  

‘We suspect that this form of hereditary frontotemporal dementia starts with a disruption of the blood-brain barrier. You need this to allow the brain to function properly,' says Van Swieten of Erasmus. According to the researchers, these results mean that follow-up research into a possible treatment should focus on the blood-brain barrier.   

About frontotemporal dementia  

  • After Alzheimer's disease, frontotemporal dementia is the most common form of dementia in people younger than 65 years.   

  • The first symptoms, such as behavioural changes, often appear between the ages of 40 and 60.  

  • About 30% of FTD patients have a hereditary form.   

  • There is no cure for frontotemporal dementia.