New Protein Linked to Early-Onset Dementia Identified

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.

In a paper published in the journal Nature, research led by scientists from the Medical Research Council (MRC) Laboratory of Molecular Biology, 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 scientists used cutting-edge cryo-electron microscopy (cryo-EM) to study protein aggregates from the brains of four people who had this type of frontotemporal dementia at atomic resolution.

In this type of dementia, scientists had long thought that a protein called FUS aggregated, based on similarities with other neurodegenerative diseases.

Using cryo-EM, the researchers at the MRC Laboratory of Molecular Biology were able to identify that the protein aggregates from each brain had the same atomic structure.

Surprisingly, the protein was not FUS — it was another protein called TAF15.

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.

Sources:

Tetter, S., Arseni, D., Murzin, A.G. et al. TAF15 amyloid filaments in frontotemporal lobar degeneration. Nature, 2023 DOI: 10.1038/s41586-023-06801-2

UK Research and Innovation. (2023, December 6). New protein linked to early-onset dementia identified. ScienceDaily. Retrieved December 6, 2023 from www.sciencedaily.com/releases/2023/12/231206115845.htm

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