Researchers have discovered a rare new genetic form of dementia. Similar to Alzheimer’s, it paves the way for new therapies targeting the accumulation of tau proteins in the brain.
- Researchers have discovered that a rare new form of dementia, called vacuolar tauopathy, is caused by a mutation in the tau protein gene.
- This, when it accumulates in certain parts of the brain, is responsible for Alzheimer’s disease.
- This finding could lead to new treatments to prevent tau protein aggregates in the brain.
“Vacuolar tauopathy”. This is the name that researchers from Penn Medicine (USA) have given to the rare new genetic form of dementia they have discovered. Characterized, like Alzheimer’s, by the accumulation of tau proteins in certain parts of the brain, it could give rise to new therapeutic leads.
In a study published in the journal Science, the researchers say they discovered this new form of dementia by examining human brain tissue samples from a deceased donor with an unknown neurodegenerative disease. There they discovered a new mutation in the valosin-containing protein (PCV) gene in the brain, an accumulation of tau proteins in degenerating areas and neurons with empty holes, called vacuoles. Hence the name given to this new neurodegenerative disease, characterized by the accumulation of neuronal vacuoles and tau protein aggregates.
“In a cell, proteins come together and you need a process to be able to separate them, otherwise everything gets dirty and doesn’t work anymore. PCV is often implicated in cases where it finds proteins in an aggregate and pulls them apart, explains Professor Edward Lee, author of the work. We believe the mutation impairs the normal ability of proteins to break up aggregates.”
A new therapeutic avenue
According to the researchers, the tau protein accumulated in vacuolar tauopathy is very similar to the tau protein aggregates observed in Alzheimer’s disease. With these similarities, they set out to find out how this PCV mutation causes this new disease. They first looked at the proteins themselves, in addition to studying cells in the lab and in an animal model. They then discovered that the accumulation of the tau protein is in fact due to the PCV mutation.
“What we found in this study is a pattern that we have never seen before, as well as a mutation that has never been described before, says Edward Lee. Given that this mutation inhibits VCP activity, this suggests that the reverse might be true: that if you are able to stimulate VCP activity, it might help break up protein aggregates.”
According to the researchers, if this hypothesis is confirmed, it means that it will not only be possible to break down tau protein aggregates for this rare form of dementia, but also for other neurodegenerative diseases, including Alzheimer’s.
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