Protein found in brain linked to frontotemporal dementia

An international team of researchers has identified a protein found in the brains of people with frontotemporal dementia (FTD), discovering a new target for potential treatments for the disease.

According to the National Institutes of Health, FTD results from damage to neurons in the frontal and temporal lobes of the brain. People with this type of dementia typically present symptoms, including unusual behaviors, emotional problems, trouble communicating, difficulty with work or in some cases difficulty with walking, between the ages of 25 and 65.

Neurodegenerative disorders, including dementias and Amyotrophic Lateral Sclerosis (ALS), occur when specific proteins form amyloid filaments in the nerve cells of the brain and spinal cord. The multidisciplinary team of researchers found that in cases of FTD, a protein called  TATA-binding protein-associated factor 15 (TAF15) forms these amyloid filaments in the cells of the brain and the spinal cord. They published their findings in Nature.
The team studied the protein aggregates from brains donated by four people who had frontotemporal dementia and motor weakness. Together with their colleagues in the UK, IU researchers used neuropathologic and molecular techniques and cutting-edge cryo-electron microscopy (cryo-EM) at atomic resolution to discover the presence of the amyloid filaments made of TAF15 protein in multiple brain areas. The filament fold is formed from residues 7–99 in the low-complexity domain (LCD) of TAF15 and was identical between individuals. However it is important to note that TAF15 amyloid affects also nerve cells of the motor system.

“This discovery represents an important breakthrough that recognizes TAF15 as a potential target for the development of diagnostic and therapeutic strategies toward a lesser-known form of frontotemporal lobar degeneration associated with frontotemporal dementia,” the author said.