Dementia faster than Alzheimer’s… “New protein discovered”

Research results have revealed that a new protein related to ‘frontotemporal dementia’, a type of dementia that appears earlier than Alzheimer’s disease, has been discovered.

The Medical Research Council (MRC) Laboratory for Molecular Biology (LMB) at the University of Cambridge, UK, has accurately identified a malignant protein (TAF15) and its aggregated structure that had not been identified as the cause of frontotemporal dementia (approximately 5-10% of dementia). revealed.

Most neurodegenerative diseases, including dementia, are related to proteins that aggregate into filaments called amyloid. In particular, Alzheimer’s disease, which accounts for the majority of dementia (50-80%), is caused by the accumulation and aggregation of amyloid-beta protein and tau protein.

Frontotemporal dementia is caused by degeneration of the frontal and temporal lobes of the brain, which control emotions, personality, behavior, language, and word comprehension. It tends to start at a younger age than Alzheimer’s disease. It is often diagnosed between the ages of 45 and 65, but it can also affect younger or older people.

“This discovery greatly advances our understanding of the molecular basis of frontotemporal dementia,” said Dr Benjamin Riskeldi-Falcon, who led the study. “We discovered a new component of a small group of proteins known to aggregate in neurodegenerative diseases.” It is now possible to target these aggregated proteins for diagnostic testing and treatment of dementia.

The research team analyzed protein aggregates from the donated brains of four patients with frontotemporal dementia using state-of-the-art cryo-electron microscopy (cryo-EM). The research team confirmed that protein aggregates in each brain had the same atomic structure. Unexpectedly, the protein was not ‘FUS’ but a different protein called ‘TAF15’.

Some patients with frontotemporal dementia also suffer from motor neuron disease, which causes them to gradually lose control of their muscles. The research team revealed that two out of four people suffered from this disease and identified aggregate structures identical to TAF15 in their brains. The presence of the same TAF15 aggregate in two people showing signs of frontotemporal dementia and motor neuron disease means that the TAF15 protein may be the cause of both diseases.

“TAF15 was not known to form amyloid filaments in neurodegenerative diseases, and the protein structure did not exist,” said Dr. Stephen Teter, first author of the study. Therefore, the results of this study are unexpected.”

He emphasized, “Cryo-EM, an ultra-low temperature electron microscope that analyzes protein structures, is playing a big role in expanding our understanding of the molecular pathology of dementia and neurodegenerative diseases by providing insight beyond the capabilities of previous technologies.” Dr. Richard Henderson, a biologist at the University of Cambridge in England, received the 2017 Nobel Prize in Chemistry for his innovations in cryogenic electron microscopy.

The research team is studying whether abnormally aggregated TAF15 exists in motor neuron disease patients without frontotemporal dementia. The results of this study (TAF15 amyloid filaments in frontotemporal lobar degeneration) were published in the international journal Nature.