Study of the Week: Do These Protein Fibrils Suggest a Connection Between Certain Neurodegenerative Diseases?

Welcome to Study of the Week from Patient Worthy. In this segment, we select a study we posted about from the previous week that we think is of particular interest or importance and go more in-depth. In this story we will talk about the details of the study and explain why it’s important, who will be impacted, and more.

If you read our short form research stories and find yourself wanting to learn more, you’ve come to the right place.

 

This week’s study is…

Homotypic fibrillization of TMEM106B across diverse neurodegenerative diseases

We previously published about this research in a story titled “Study: TMEM106B Protein Linked to PSP, LBD, FTD” which can be found here. This study was first published in the scientific journal Cell. You can view the full text of the study here.

What Happened?

Neurodegenerative diseases continue to present a major challenge to modern medicine, with almost no illnesses in this category having particularly effective therapies that can slow progression, stop progression, or cure them. As a result, scientists around the world are studying them closely in order to gain new insights that could lead to better treatments in the future. In this study, an international research team identified protein fibrils that were found in three different neurodegenerative illnesses: frontotemporal dementia, dementia with Lewy bodies, and progressive supranuclear palsy. 

These conditions are classified as proteinopathies, in which filamentous protein aggregations are deposited in glia or neurons; this activity is believed to play a central role in the mechanism of these diseases. The research team analyzed protein extracted from 11 patients that had been diagnosed with either dementia with Lewy bodies, frontotemporal dementia, or progressive supranuclear palsy.

While each of these disorders has a unique protein fibril associated with it, the scientists also found something that they did not initially expect: another form of protein fibrils. These were found in samples from all three diseases and were believed to be caused by a protein called TMEM106B, which normally is a component of lysosomes and and endosomes. Ironically, these organelles typically help clear out debris that accumulates in cells.

The scientists used an approach called cryo-electron microscopy in order to analyze the structure of these new protein fibrils. While these findings do not definitively demonstrate that TMEM106B fibrils are a direct cause of these neurogenerative illnesses, their presence in samples from multiple neurogenerative illnesses could be important and warrants further investigation.

About Progressive Supranuclear Palsy (PSP)

Progressive supranuclear palsy is a type of neurodegenerative disease which is most characterized by the deterioration and death of certain areas of the brain over time. Symptoms include falling, bumping into other objects, a distinctive lunging movement when walking begins, difficulty controlling eye movement, slowing of movements, vision problems, cognitive impairment, and dystonia affecting the neck. There is no cure, and treatment is primarily supportive; management includes physical therapy to delay loss of mobility. In some cases, the Parkinson’s drug levodopa can be effective. To learn more about progressive supranuclear palsy, click here.

About Frontotemporal Dementia

Frontotemporal dementia are forms of dementia mostly impacting the temporal and frontal lobes of the brain. These are early onset forms of dementia, often before age 60-65. Symptoms include loss of emotional control, compulsive buying disorder, family dissociation, vulgar speech, yelling, and other changes to personality, behavior, and temperament. Some treatments can help manage the behavioral symptoms, such as SSRIs. However, there is no cure for frontotemporal dementia. Survival after diagnoses ranges widely, from two to 20 years. To learn more about these dementias, click here.

About Dementia With Lewy Bodies

Dementia with Lewy bodies is a form of dementia that causes changes to autonomic function, sleep, movement, cognition, and behavior. While dementia in general is often associated with memory loss, this is not often an early symptom in this form. Other symptoms include visual hallucinations, fluctuations in alertness and attention, and parkinsonism. While certain medications can help treatment some of the symptoms, none have been found that can cure the disease or slow its progression. Dementia with Lewy bodies can be more severe than other types and often progresses rapidly; survival time following diagnosis averages around four years, but can vary considerably. To learn more about this disease, click here.

Why Does it Matter?

The identification of protein fibrils that were likely caused by TMEM106B in three different neurodegenerative illnesses raises some questions and could potentially point to a shared mechanism between the three diseases. It’s possible that future research into these fibrils could help lead to a greater understanding of neurodegenerative illnesses and even a potential treatment approach. However, the scientists still note that the presence of the fibrils could also simply be a general characteristic of neurodegeneration or aging.

It’s also worth noting that prior studies did not find these fibrils in other neurodegenerative diseases, like corticobasal degeneration or Alzheimer’s.

“We now have a promising new lead…it could point towards a common thread linking a range of neurodegenerative diseases and could open the way to new interventions.” – Anthony W.P. Fitzpatrick, Ph.D, Columbia University, Lead Researcher

 

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