A Common Link Between Several Neurodegenerative Diseases Might Finally Be Identified

Misfolded proteins clump together to form sticky plaques or tangles, which are a hallmark of neurodegenerative diseases.

A group of common and rare neurodegenerative diseases, including two distinct forms of dementia, might be a result of a common feature of aprotein normally tasked with clearing cells ofmolecular debris.

According to the team behind the study, the finding was both unexpected and surprising, and raises many intriguing questions.

The biophysicist says that they have found that aProtein called TMEM106B can form fibrils, and this behavior was not known before.

Frontotemporal dementia is the most common form of dementia for people under the age of 60, and progressive supranuclear palsy is a rare brain disorder which impairs balance, walking and vision.

Structural Biologist Anthony Fitzpatrick of Columbia University says that each of the diseases has a unique fibril.

Some previously undetected fibrils were found in all 11 post-mortem brain samples.

To investigate, the researchers used a technique called cryo-electron microscopy, which involves flash-freezing proteins to capture the fine details of their shape and structure, and is capable of resolving smaller features.

In the cases of frontotemporal dementia, the narrow twisted rods and wide twisted ribbons were formed by the fragments of the mysteriousprotein.

The researchers inferred the most probable sequence of the building blocks based on the structures. They scanned a database and found fragments that were similar to one that had been identified more than a decade ago.

The lysosomes and endosomes have two types of cell substructures, one of which is the TMEM106B.

Brain tissue samples have images of fibrils in them.

The TMEM106B is thought to disrupt lysosome function by forming fibrils. This leads to a build-up of other fibril-forming proteins, which is implicated in Alzheimer's disease.

The data doesn't show that TMEM106B causes neurodegenerative disease, only that it happens to be present in the brain tissue of a few people with different diseases.

It is difficult to determine whether TMEM106B fibrils are disease specific or are a general feature of neurodegeneration and aging, because they occur across diverse proteinopathies. A recent study found TMEM106B in the brains of healthy older adults but not younger individuals.

Fitzpatrick and colleagues didn't detect the TMEM106B fibrils in their previous studies of Alzheimer's disease and corticobasal degeneration. It may reflect the small number of brain samples analyzed so far.

Fitzpatrick and colleagues suspect that the presence of TMEM106B fibrils could amplify or accelerate the build up of pathological proteins.

Fitzpatrick says that they now have a promising new lead.

Many failed trials and much disappointment have been caused by decades of research into therapies targeting the amyloid-beta.

There may be some similarities between neurodegenerative diseases, but their individual root causes remain elusive.

The study was published in a journal.