Unexpected Protein Linked to Early-Onset Dementia in Huge Discovery

Good news!

Perhaps, it is not too late to get some treatment for the senile, demented and corrupt 46th President!

"Scientists have singled out which protein forms the characteristic clumps of a type of early-onset dementia where no firm suspect was known before.

This discovery reportedly transforms understanding of the molecular basis of frontotemporal dementia (FTD), the second-most common form of dementia after Alzheimer's, with symptoms typically emerging earlier: in a person's late 40s or 50s. ..."

"Scientists have identified abnormal aggregates of a protein called TAF15 in the brains of individuals with early-onset dementia ...
Most neurodegenerative diseases, including dementias, involve proteins aggregating into filaments called amyloids. ...
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. ..."

"... The neurodegenerative disorder frontotemporal lobar degeneration (FTLD) causes frontotemporal dementia, the most common form of dementia after Alzheimer’s disease. Yet, in approximately 10% of cases of FTLD, the filament forming protein was unknown. The filaments were widely assumed to be formed by the protein FUS, due to the presence of this protein in the brain inclusions and genetic evidence for its role in rare cases of another neurodegenerative disorder, amyotrophic lateral sclerosis. ...
This work uncovers the molecular pathology of this type of FTLD. It represents a rare finding of a new member of the small group of proteins known to form neurodegenerative disease-associated amyloid filaments, alongside proteins such as amyloid-b, tau, TDP-43 and a-synuclein. The study establishes TAF15 as a target for the diagnosis and treatment of neurodegenerative disease. ..."

From the abstract:

"Frontotemporal lobar degeneration (FTLD) causes frontotemporal dementia (FTD), the most common form of dementia after Alzheimer’s disease, and is often also associated with motor disorders. The pathological hallmarks of FTLD are neuronal inclusions of specific, abnormally assembled proteins. In the majority of cases the inclusions contain amyloid filament assemblies of TAR DNA-binding protein 43 (TDP-43) or tau, with distinct filament structures characterizing different FTLD subtypes. The presence of amyloid filaments and their identities and structures in the remaining approximately 10% of FTLD cases are unknown but are widely believed to be composed of the protein fused in sarcoma (FUS, also known as translocated in liposarcoma). As such, these cases are commonly referred to as FTLD–FUS. Here we used cryogenic electron microscopy (cryo-EM) to determine the structures of amyloid filaments extracted from the prefrontal and temporal cortices of four individuals with FTLD–FUS. Surprisingly, we found abundant amyloid filaments of the FUS homologue TATA-binding protein-associated factor 15 (TAF15, also known as TATA-binding protein-associated factor 2N) rather than of FUS itself. The filament fold is formed from residues 7–99 in the low-complexity domain (LCD) of TAF15 and was identical between individuals. Furthermore, we found TAF15 filaments with the same fold in the motor cortex and brainstem of two of the individuals, both showing upper and lower motor neuron pathology. The formation of TAF15 amyloid filaments with a characteristic fold in FTLD establishes TAF15 proteinopathy in neurodegenerative disease. The structure of TAF15 amyloid filaments provides a basis for the development of model systems of neurodegenerative disease, as well as for the design of diagnostic and therapeutic tools targeting TAF15 proteinopathy."

Unexpected Protein Linked to Early-Onset Dementia in Huge Discovery : ScienceAlert

New protein linked to early-onset dementia identified Researchers have established a first potential therapeutic target for a type of early-onset dementia.

Discovery of a new amyloid-forming protein in neurodegenerative disease It was widely assumed that pathological amyloid filaments in certain cases of frontotemporal lobar degeneration are formed by the protein FUS, but cryo-EM has unexpectedly revealed that they are instead formed by the protein TAF15.

TAF15 amyloid filaments in frontotemporal lobar degeneration (open access)

Extended Data Fig. 5: A high-resolution map of TAF15 amyloid filaments from FTLD-FET.