Something goes wrong with the blood-brain barrier of patients with a certain hereditary form of frontotemporal dementia (FTD). Researchers from the UMCG and Erasmus MC discovered this, who published their study in the scientific journal Nature Neuroscience.
Progranuline-gen
Patients with frontotemporal dementia develop symptoms of dementia at a relatively early age. The hereditary form of FTD is caused in thirty percent of cases by a mutation in the progranulin gene. Nothing was known about what exactly goes wrong in the brains of people with this hereditary form of FTD. Previous research suggested the brain’s immune cells might play a role, but the new research points in a different direction.
Compare brain tissues
The Rotterdam and Groningen researchers compared brain tissue from thirteen FTD patients with the progranulin mutation with brain tissue from seven deceased people without brain disease. The researchers studied cells other than the nerve cells in great detail. ‘We used a technique called single-nucleus RNA sequencing, a way to determine which genes are active in individual cells. The question was: has that changed at FTD?’, explains neuroscientist Prof. Bart Eggen of the UMCG. He led the research together with neurologist Prof. Dr. John van Swieten of Erasmus MC.
Disruption of the blood-brain barrier
The researchers found signs of disease in particular 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 stops harmful substances. The immune cells or 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. It is therefore not surprising that a progranulin mutation also leads to problems with the blood vessels in the brain.
‘We suspect that this form of hereditary frontotemporal dementia starts with a disruption of the blood-brain barrier. You need them to keep the brain functioning properly’, says Van Swieten of Erasmus MC.
Follow-up research
According to the researchers, these results mean that further research into a possible treatment should focus on the blood-brain barrier.
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