New Protein Linked To Early-Onset Dementia Identified
Researchers have established a first potential therapeutic target for a type of early-onset dementia.
Scientists have identified abnormal aggregates of a protein called TAF15 in the brains of individuals with early-onset dementia, known as frontotemporal dementia, where the cause was not previously known.
Most neurodegenerative diseases, including dementias, involve proteins aggregating into filaments called amyloids. In most of these diseases, researchers have identified the proteins that aggregate, allowing them to target these proteins for diagnostic tests and treatments.
But, in around 10% of cases of frontotemporal dementia, scientists had yet to identify the rogue protein. Now, scientists have pinpointed aggregated structures of the protein TAF15 in these cases.
Frontotemporal dementia results from the degeneration of the frontal and temporal lobes of the brain, which control emotions, personality and behaviour, as well speech and understanding of words. It tends to start at a younger age than Alzheimer’s disease, often being diagnosed in people aged 45 to 65, although it can also affect younger or older people.
A team of researchers led by scientists from the Medical Research Council (MRC) Laboratory of Molecular Biology (LMB), in Cambridge, UK, has identified aggregated structures of a protein that could provide a target for the future development of diagnostic tests and treatments. The research is published in the journal ‘Nature’ today.
Dr Benjamin Ryskeldi-Falcon, who led the study at the MRC LMB, said: “This discovery transforms our understanding of the molecular basis of frontotemporal dementia. It is a rare finding of a new member of the small group of proteins known to aggregate in neurodegenerative disease.”
“Now that we have identified the key protein and its structure, we can start to target it for the diagnosis and therapy of this type of frontotemporal dementia, similar to strategies already in the pipeline for targeting the aggregates of amyloid-beta and tau proteins that characterise Alzheimer’s disease.”
Some people who have frontotemporal dementia also have motor neuron disease, a condition in which individuals progressively lose control over their muscles. In this study, two of the individuals who donated their brains had signs of both diseases. For these individuals, the researchers identified the same aggregated structure of TAF15 in brain regions associated with motor neuron disease.
Dr Ryskeldi-Falcon said: “The presence of the same TAF15 aggregates in two individuals who had frontotemporal dementia and signs of motor neuron disease raises the possibility that TAF15 may contribute to both diseases. We are now studying whether aberrant aggregated TAF15 is present in people who have motor neurone disease in the absence of frontotemporal dementia.”
